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1.
Clin Exp Rheumatol ; 39 Suppl 130(3): 108-114, 2021.
Article in English | MEDLINE | ID: covidwho-1819217

ABSTRACT

OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors. METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment. RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01). CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.


Subject(s)
COVID-19 , Fibromyalgia , Anxiety/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Depression/epidemiology , Disease Outbreaks , Fibromyalgia/diagnosis , Fibromyalgia/epidemiology , Fibromyalgia/therapy , Humans , SARS-CoV-2 , Surveys and Questionnaires
2.
Rev Esp Cardiol ; 74(7): 608-615, 2021 Jul.
Article in Spanish | MEDLINE | ID: covidwho-1805063

ABSTRACT

INTRODUCTION AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Atrial fibrillation (AF) is common in acute situations, where it is associated with more complications and higher mortality. METHODS: Analysis of the international HOPE registry (NCT04334291). The objective was to assess the prognostic information of AF in COVID-19 patients. A multivariate analysis and propensity score matching were performed to assess the relationship between AF and mortality. We also evaluated the impact on mortality and embolic events of the CHA2DS2-VASc score in these patients. RESULTS: Among 6217 patients enrolled in the HOPE registry, 250 had AF (4.5%). AF patients had a higher prevalence of cardiovascular risk factors and comorbidities. After propensity score matching, these differences were attenuated. Despite this, patients with AF had a higher incidence of in-hospital complications such as heart failure (19.3% vs 11.6%, P = .021) and respiratory insufficiency (75.9% vs 62.3%, P = .002), as well as a higher 60-day mortality rate (43.4% vs 30.9%, P = .005). On multivariate analysis, AF was independently associated with higher 60-day mortality (hazard ratio, 1.234; 95%CI, 1.003-1.519). CHA2DS2-VASc score acceptably predicts 60-day mortality in COVID-19 patients (area ROC, 0.748; 95%CI, 0.733-0.764), but not its embolic risk (area ROC, 0.411; 95%CI, 0.147-0.675). CONCLUSIONS: AF in COVID-19 patients is associated with a higher number of complications and 60-day mortality. The CHA2DS2-VASc score may be a good risk marker in COVID patients but does not predict their embolic risk.

3.
Pain Rep ; 5(6): e858, 2020.
Article in English | MEDLINE | ID: covidwho-1794976

ABSTRACT

INTRODUCTION: The SARS-Cov-2 pandemic requires special attention on its psychological effects and the impact on patients with chronic pain. OBJECTIVES: This study aimed at examining the influence of the COVID-19 pandemic-associated regulations initiated by the German government on pain intensity and characteristics, emotional well-being, and everyday life of patients with painful polyneuropathy. METHODS: Forty-three patients (well assessed with questionnaires before the pandemic and without change of their health status between baseline and current assessment) were investigated with validated, self-reported questionnaires and COVID-19-specific items 2 weeks after the regulations came into effect. RESULTS: Pain intensity remained stable or even improved like the neuropathic pain symptom inventory total score (t0: 33.54 ± 20.48 vs t1: 27.38 ± 16.16, P = 0.008). Only 11.6% reported a pandemic-associated pain worsening. Rumination scores of the Pain Catastrophizing Scale were lower during t1 compared to before the pandemic regulations (t0: 7.81 ± 4.70, t1: 6.49 ± 4.39; P = 0.030). Interestingly, pain ratings for the last 7 days were higher in patients with a changed social life compared to those without (-1.63 ± 1.60 vs 0.31 ± 1.83; P = 0.01). Quality of life was decreased and helplessness increased in those with higher pain ratings. CONCLUSION: Results suggest a shift of attention from the chronic pain condition towards the imminent threat of a global pandemic. As the impacts of the pandemic are persistent and evolving, the development of the measured parameters in the forthcoming weeks will be of great interest.

4.
Minerva Cardiol Angiol ; 70(2): 160-166, 2022 04.
Article in English | MEDLINE | ID: covidwho-1786557

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has rapidly spread globally. Due to different testing strategies, under-detection of positive subjects and COVID-19-related-deaths remains common. Aim of this analysis was to assess the real impact of COVID-19 through the analysis of 2020 Italian all-cause mortality data compared to historical series. METHODS: We performed a retrospective analysis of 2020 and 2015-2019 all-cause mortality data released by the Italian National Institute for Statistics (ISTAT) for the time period January 1st-March 21st. This preliminary sample included 1084 Italian municipalities showing at least 10 deaths during the above-mentioned timeframe and an increase in mortality of more than 20% as compared to the previous five years (2015-2019), with a resulting coverage of 21% of Italian population. The difference between 2020 observed and expected deaths (mean of weekly deaths in 2015-2019) was computed, together with mortality rate ratio (MRR) for each of the four weeks following detection of the first autochthonous COVID-19 case in Italy (February 23rd, 2020 - March 21st, 2020), as well as for this entire timeframe. Subgroup analysis by age groups was also performed. RESULTS: Overall MRR was 1.79 [1.75-1.84], with an observed excess mortality of 8750 individuals in the investigated sample, which in itself outweighs Italian Civil Protection report of only 4,825 COVID-19-related deaths across Italy, as of March 21. Subgroup analysis did not show any difference in mortality rate in '0-14 years' age group, while MRRs were significantly increased in older age groups, in particular in patients >75 years (MRR 1.84 [1.79-1.89]). In addition, week-by-week analysis showed a progressive increase in MRR during this period, peaking in the last week (March 15th, 2020 - March 21st, 2020) with an estimated value of 2.65 [2.53-2.78]. CONCLUSIONS: The analysis of all-cause mortality data in Italy indicates that reported COVID-19-related deaths are an underestimate of the actual death toll. All-cause death should be seen as the epidemiological indicator of choice to assess the real mortality impact exerted by SARS-CoV-2, given that it also best reflects the toll on frail patient subsets (e.g. the elderly or those with cardiovascular disease).


Subject(s)
COVID-19 , Cardiovascular Diseases , Aged , Cardiovascular Diseases/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
5.
Cell Host Microbe ; 27(6): 879-882.e2, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-1719463

ABSTRACT

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.


Subject(s)
Coronavirus Infections/genetics , Coronavirus Infections/immunology , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Adult , Aged , Biological Variation, Individual , COVID-19 , Cluster Analysis , Coronavirus Infections/blood , Coronavirus Infections/pathology , Cytokines/blood , Gene Expression Regulation , Humans , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Transcriptome , Up-Regulation
8.
Pediatr Infect Dis J ; 40(7): 606-611, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1709106

ABSTRACT

BACKGROUND: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. METHODS: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. RESULTS: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CONCLUSION: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.


Subject(s)
COVID-19/therapy , Adolescent , Antibodies, Viral/blood , Child , Child, Preschool , Female , Humans , Immunization, Passive/standards , Immunization, Passive/statistics & numerical data , Immunoglobulin G/blood , Infant , Infant, Newborn , Kinetics , Male , Prospective Studies , Retrospective Studies
9.
Pediatr Int ; 64(1): e14890, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1700184

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) in children is milder than in adults. Household virus exposure may affect clinical severity. We aimed to determine the household contact history of patients and its influence on the clinical stage. METHODS: One hundred and seventy-three pediatric patients with COVID-19 as diagnosed with positive real-time polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 aged 1 month to 18 years were included. Demographic data, laboratory and clinical findings, and the history of household contact of the patients were obtained. They were classified according to their clinical stage as mild or moderate-severe. RESULTS: Sixty patients (34.7%) were asymptomatic, and 113 were symptomatic (65.3%). Of the 173 patients, 138 (79.8%) had at least one family member in the household who was diagnosed as having COVID-19. Hemoglobin, absolute neutrophil count, and absolute neutrophil count /absolute lymphocyte count ratio decreased significantly in patients with household contact. The presence of a household contact did not have a significant effect on the presence of symptoms, clinical course, age, and the sex of the patients. The need for hospitalization was less in the group that had household contact. Being 0-12 months, being female, and being a patient without household contact were independent factors associated with higher hospitalization ratios in logistic regression analysis. CONCLUSIONS: In this study, we found that household contact history did not significantly affect presenting symptoms and clinical course. We detected the rate of hospitalization to be less in the group with only household contact.


Subject(s)
COVID-19 , Adult , Child , Family Characteristics , Female , Humans , SARS-CoV-2
10.
Mol Cells ; 44(6): 401-407, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1687545

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4+ and CD8+ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.


Subject(s)
Antibodies, Neutralizing/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/pathogenicity , Antibodies, Viral/biosynthesis , CD4-Positive T-Lymphocytes/classification , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/classification , CD8-Positive T-Lymphocytes/virology , COVID-19/pathology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Convalescence , Cytokines/biosynthesis , Cytotoxicity, Immunologic , Host-Pathogen Interactions/immunology , Humans , Immunity, Humoral , Immunologic Memory , Immunophenotyping , SARS-CoV-2/immunology , Severity of Illness Index
11.
Cell Rep Med ; 2(5): 100287, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1683718

ABSTRACT

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

12.
Lancet ; 397(10289): 2049-2059, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1671320

ABSTRACT

BACKGROUND: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79). INTERPRETATION: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
COVID-19/therapy , Hospital Mortality , Length of Stay/statistics & numerical data , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/mortality , Female , Humans , Immunization, Passive/methods , Immunization, Passive/mortality , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Treatment Outcome , United Kingdom/epidemiology
13.
Clin Infect Dis ; 74(2): 254-262, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1662114

ABSTRACT

BACKGROUND: Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. METHODS: Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity. RESULTS: Interleukin-18 (IL-18), IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. CONCLUSIONS: These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.


Subject(s)
COVID-19 , Influenza, Human , Chemokines , Cytokines , Humans , SARS-CoV-2
14.
Clin Infect Dis ; 74(2): 327-334, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1662105

ABSTRACT

Convalescent plasma (CP) have been used for treatment of coronavirus disease 2019 (COVID-19), but their effectiveness varies significantly. Moreover, the impact of CP treatment on the composition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 patients and antibody markers that differentiate between those who survive and those who succumb to the COVID-19 disease are not well understood. Herein, we performed longitudinal analysis of antibody profile on 115 sequential plasma samples from 16 hospitalized COVID-19 patients treated with either CP or standard of care, only half of them survived. Differential antibody kinetics was observed for antibody binding, immunoglobulin M/immunoglobulin G/immunoglobulin A (IgM/IgG/IgA) distribution, and affinity maturation in "survived" versus "fatal" COVID-19 patients. Surprisingly, CP treatment did not predict survival. Strikingly, marked decline in neutralization titers was observed in the fatal patients prior to death, and convalescent plasma treatment did not reverse this trend. Furthermore, irrespective of CP treatment, higher antibody affinity to the SARS-CoV-2 prefusion spike was associated with survival outcome. Additionally, sustained elevated IgA response was associated with fatal outcome in these COVID-19 patients. These findings propose that treatment of COVID-19 patients with convalescent plasma should be carefully targeted, and effectiveness of treatment may depend on the clinical and immunological status of COVID-19 patients, as well as the quality of the antibodies in the convalescent plasma.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive
15.
Ann Clin Biochem ; 59(1): 15-22, 2022 01.
Article in English | MEDLINE | ID: covidwho-1622156

ABSTRACT

BACKGROUND: There is limited information regarding the role of biomarker levels at predicting mortality in patients with the coronavirus disease (COVID-19) pandemic. The purpose of this study is to determine the differences in serum biomarker levels in adults with COVID-19 who survived hospitalization from those who did not. METHODS: A comprehensive search was completed on PubMed, EMBASE and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. RESULTS: A total of 10 studies with 1584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from coronavirus disease included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukin-6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Lymphocyte count, platelet count and albumin were significantly lower in patients who died. CONCLUSION: This pooled analysis of 10 studies including 1584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited health-care resources.


Subject(s)
COVID-19 , Biomarkers , C-Reactive Protein/analysis , Humans , Leukocyte Count , Pandemics , Retrospective Studies , SARS-CoV-2
16.
Clin Infect Dis ; 74(1): 59-65, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621577

ABSTRACT

BACKGROUND: Several vaccines are now available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. Vaccine impact on asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is largely unknown. METHODS: We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39 156) within a large US healthcare system who underwent 48 333 preprocedural SARS-CoV-2 molecular screening tests between 17 December 2020 and 8 February 2021. The primary exposure of interest was vaccination with ≥1 dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk (RR) of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received ≥1 dose of vaccine compared with persons who had not received vaccine during the same time period. RR was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs nonlocal), healthcare system regions, and repeated screenings among patients using mixed-effects log-binomial regression. RESULTS: Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3006 tests and 1436 (3.2%) of 45 327 tests performed on vaccinated and unvaccinated patients, respectively (RR, .44; 95% CI, .33-.60; P < .0001). Compared with unvaccinated patients, risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after the first dose (RR, .21; 95% CI, .12-.37; P < .0001) and >0 days after the second dose (RR, .20; 95% CI, .09-.44; P < .0001) in the adjusted analysis. CONCLUSIONS: COVID-19 vaccination with an mRNA-based vaccine showed a significant association with reduced risk of asymptomatic SARS-CoV-2 infection as measured during preprocedural molecular screening. Results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.


Subject(s)
COVID-19 , Adult , Asymptomatic Infections/epidemiology , COVID-19 Vaccines , Humans , Retrospective Studies , SARS-CoV-2 , United States
17.
PLoS One ; 16(3): e0247797, 2021.
Article in English | MEDLINE | ID: covidwho-1605332

ABSTRACT

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31-60 days PSO. By 61-90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1-4 days PSO with 86% positivity observed at 5-7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Serological Testing/instrumentation , COVID-19 Serological Testing/methods , Equipment Design , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2/isolation & purification , Young Adult
18.
Ann Med ; 53(1): 181-188, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575964

ABSTRACT

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients' CD8+ T cells and D-dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS. CONCLUSIONS: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Blood Coagulation/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Dose-Response Relationship, Drug , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Heparin/administration & dosage , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Linear Models , Longitudinal Studies , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Middle Aged , Models, Biological , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Time-to-Treatment , Young Adult
19.
Rev Med Virol ; 31(5): 1-12, 2021 09.
Article in English | MEDLINE | ID: covidwho-1575376

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) receptor. Other important proteins involved in this process include disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) also known as tumour necrosis factor-α-converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1-7), to balance the renin angiotensin system. Membrane-bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS-CoV-2 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non-primed virus-sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II-angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , ADAM17 Protein/genetics , ADAM17 Protein/metabolism , Angiotensin I/metabolism , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/genetics , COVID-19/virology , Comorbidity , Humans , Peptide Fragments/metabolism , SARS-CoV-2/physiology
20.
Int J Infect Dis ; 113 Suppl 1: S82-S87, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1575296

ABSTRACT

OBJECTIVES: The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI). METHODS: We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). RESULTS: We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178). CONCLUSIONS: Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.


Subject(s)
COVID-19 , Coinfection , Tuberculosis , Antigens, Bacterial/immunology , Antigens, Viral/immunology , COVID-19/immunology , Humans , Interferon-gamma/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tuberculosis/immunology
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