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1.
J Am Heart Assoc ; 9(22): e017364, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-2064368

ABSTRACT

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme-2 (ACE-2) receptor to enter human cells. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID-19). Methods and Results We used the Coracle registry, which contains data of patients hospitalized with COVID-19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in-hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (PTrend<0.0001). The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% CI, 0.60-1.60, P=0.9333, and 1.13, 95% CI, 0.67-1.91, P=0.6385, respectively. After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR, 0.55; 95% CI, 0.31-0.98, P=0.0436); a similar, but weaker trend was observed for ARB administration (OR, 0.58; 95% CI, 0.32-1.07, P=0.0796). Conclusions In those aged ≥50 years hospitalized with COVID-19, antecedent use of ACEI was independently associated with reduced risk of inpatient death. Our findings suggest a protective role of renin-angiotensin-aldosterone system inhibition in patients with high cardiovascular risk affected by COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/therapy , Hospitalization , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Protective Factors , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
2.
J Am Coll Emerg Physicians Open ; 1(4): 569-577, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1898677

ABSTRACT

Background: The SARS-CoV-2 (COVID-19) virus has wide community spread. The aim of this study was to describe patient characteristics and to identify factors associated with COVID-19 among emergency department (ED) patients under investigation for COVID-19 who were admitted to the hospital. Methods: This was a retrospective observational study from 8 EDs within a 9-hospital health system. Patients with COVID-19 testing around the time of hospital admission were included. The primary outcome measure was COVID-19 test result. Patient characteristics were described and a multivariable logistic regression model was used to identify factors associated with a positive COVID-19 test. Results: During the study period from March 1, 2020 to April 8, 2020, 2182 admitted patients had a test resulted for COVID-19. Of these patients, 786 (36%) had a positive test result. For COVID-19-positive patients, 63 (8.1%) died during hospitalization. COVID-19-positive patients had lower pulse oximetry (0.91 [95% confidence interval, CI], [0.88-0.94]), higher temperatures (1.36 [1.26-1.47]), and lower leukocyte counts than negative patients (0.78 [0.75-0.82]). Chronic lung disease (odds ratio [OR] 0.68, [0.52-0.90]) and histories of alcohol (0.64 [0.42-0.99]) or substance abuse (0.39 [0.25-0.62]) were less likely to be associated with a positive COVID-19 result. Conclusion: We observed a high percentage of positive results among an admitted ED cohort under investigation for COVID-19. Patient factors may be useful in early differentiation of patients with COVID-19 from similarly presenting respiratory illnesses although no single factor will serve this purpose.

3.
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
4.
J Cardiovasc Nurs ; 36(6): 595-598, 2021.
Article in English | MEDLINE | ID: covidwho-1706374

ABSTRACT

BACKGROUND: The COVID-19 pandemic has altered catheterization laboratory (cath lab) practices in diverse ways. OBJECTIVE: The aim of this study was to understand the impact of COVID-19 on Veterans Affairs (VA) procedural volume and cath lab team experience. METHODS: Procedural volume and COVID-19 patient data were obtained from the Clinical, Assessment, Reporting and Tracking Program. A mixed methods survey was emailed to VA cath lab staff asking about the COVID-19 response. Descriptive and manifest content analyses were conducted. RESULTS: Procedural volume decreased from April to September 2020. One hundred four patients with known COVID-19 were treated. Survey response rate was 19% of staff (n = 170/902) from 83% of VA cath labs (n = 67/81). Reassignment to other units, confusion regarding COVID-19 testing, personal protective equipment use, and low patient volume were reported. Anxiety, burnout, and leadership's role on team morale were described. CONCLUSIONS: Some teams adapted. Others expressed frustration over the lack of control over their practice. Leaders should routinely assess staff needs during the current and future crises.


Subject(s)
COVID-19 , Veterans , COVID-19 Testing , Catheterization , Humans , Laboratories , Pandemics , SARS-CoV-2 , United States
5.
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
6.
Trials ; 22(1): 172, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1622253

ABSTRACT

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials, Phase II as Topic , Disease Progression , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Humans , Length of Stay , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/etiology , SARS-CoV-2
7.
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
8.
Clin Infect Dis ; 73(11): e4179-e4188, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561122

ABSTRACT

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. METHODS: We conducted a cohort study using South Korea's nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. RESULTS: Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13-2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96-2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49-4.14). CONCLUSIONS: While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cohort Studies , Female , Hospital Mortality , Hospitalization , Humans , Middle Aged , SARS-CoV-2
9.
J Clin Pathol ; 74(12): 796-803, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1526518

ABSTRACT

AIMS: Hospitalised patients with COVID-19 have a variable incidence of acute kidney injury (AKI) according to studies from different nationalities. The present systematic review and meta-analysis describes the incidence of AKI, need for renal replacement therapy (RRT) and mortality among patients with COVID-19-associated AKI. METHODS: We systematically searched electronic database PubMed, SCOPUS and Web of Science to identify English articles published until 25 May 2020. In case of significant heterogeneity, the meta-analyses were conducted assuming a random-effects model. RESULTS: From 746 screened publications, we selected 21 observational studies with 15 536 patients with COVID-19 for random-effects model meta-analyses. The overall incidence of AKI was 12.3% (95% CI 7.3% to 20.0%) and 77% of patients with AKI were critically ill (95% CI 58.9% to 89.0%). The mortality among patients with AKI was 67% (95% CI 39.8% to 86.2%) and the risk of death was 13 times higher compared with patients without AKI (OR=13.3; 95% CI 6.1 to 29.2). Patients with COVID-19-associated AKI needed for RRT in 23.4% of cases (95% CI 12.6% to 39.4%) and those cases had high mortality (89%-100%). CONCLUSION: The present study evidenced an incidence of COVID-19-associated AKI higher than previous meta-analysis. The majority of patients affected by AKI were critically ill and mortality rate among AKI cases was high. Thus, it is extremely important for health systems to be aware about the impact of AKI on patients' outcomes in order to establish proper screening, prevention of additional damage to the kidneys and adequate renal support when needed.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/epidemiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Critical Illness , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Renal Replacement Therapy , Risk Assessment , Risk Factors
10.
Front Cardiovasc Med ; 7: 593061, 2020.
Article in English | MEDLINE | ID: covidwho-1485041

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus has spread all over the world affecting tens of millions of people. Another pandemic affecting the modern world, type 2 diabetes mellitus is among the major risk factors for mortality from COVID-19. Current evidence, while limited, suggests that proper blood glucose control may help prevent exacerbation of COVID-19 even in patients with type 2 diabetes mellitus. Under current circumstances where the magic bullet for the disease remains unavailable, it appears that the role of blood glucose control cannot be stressed too much. In this review the profile of each anti-diabetic agent is discussed in relation to COVID-19.

11.
Caspian J Intern Med ; 11(Suppl 1): 566-568, 2020.
Article in English | MEDLINE | ID: covidwho-1389947

ABSTRACT

BACKGROUND: The clinical presentation of SARS-CoV-2 infection was initially dominated by respiratory symptoms. However, the clinical spectrum is wide and neuropsychiatric syndromes are also a source of medical concern. Our aims are to present an atypical clinical presentation of SARS-CoV-2 infection characterized by auditory hallucinations and unusual behavior and to emphasize the diversity of clinical manifestations of SARS-CoV-2 infection. CASE PRESENTATION: A 33-year-old woman was admitted to the emergency department (ED) with a one-day history of auditory hallucinations, unusual behavior, changes in her sleeping habits and incoherent speech. No other symptoms were reported. Blood examinations confirmed high elevated white cell count and C-reactive protein. The head CT scan was normal but the chest scan showed right ground-glass opacities in the lower zones. The oropharyngeal swab was positive for SARS-CoV-2. Based on these results, the diagnosis of SARS-CoV-2 infection was retained. The patient received no specific treatment for SARS-CoV-2 infection and only needed oxygen therapy support for 7 days. The additional dose of Olanzapine 10 mg daily was initially prescribed but the patient was back to her usual self on day 14 of hospital admission leading to its discontinuation. This clinical course was consistent with a first episode of psychosis triggered by SARS-CoV-2 infection. CONCLUSION: Neuroinflammation owing to SARS-CoV-2 infection could be responsible for a wide and unknown spectrum of neuropsychiatric manifestations. During this pandemic, special attention should be given to patients with no previous history of psychiatric disorders presenting to ED with neuropsychiatric syndromes of unknown etiology.

12.
medRxiv ; 2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-1388081

ABSTRACT

To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

13.
J Virol ; 95(17): e0040221, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1350001

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the current coronavirus disease 2019 (COVID-19) pandemic. As of 19 May 2021, John Hopkins University's COVID-19 tracking platform reported 3.3 million deaths associated with SARS-CoV-2 infection. Currently, the World Health Organization has granted emergency use listing (EUL) to six COVID-19 vaccine candidates. However, much of the pathogenesis observed during SARS-CoV-2 infection remains elusive. To gain insight into the contribution of individual accessory open reading frame (ORF) proteins in SARS-CoV-2 pathogenesis, we used our recently described reverse-genetics system approach to successfully engineer recombinant SARS-CoV-2 (rSARS-CoV-2) constructs; we removed individual viral ORF3a, -6, -7a, -7b, and -8 proteins from them, and we characterized the resulting recombinant viruses in vitro and in vivo. Our results indicate differences in plaque morphology, with ORF-deficient (ΔORF) viruses producing smaller plaques than those of the wild type (rSARS-CoV-2/WT). However, growth kinetics of ΔORF viruses were like those of rSARS-CoV-2/WT. Interestingly, infection of K18 human angiotensin-converting enzyme 2 (hACE2) transgenic mice with the ΔORF rSARS-CoV-2s identified ORF3a and ORF6 as the major contributors of viral pathogenesis, while ΔORF7a, ΔORF7b, and ΔORF8 rSARS-CoV-2s induced pathology comparable to that of rSARS-CoV-2/WT. This study demonstrates the robustness of our reverse-genetics system to generate rSARS-CoV-2 constructs and the major role for ORF3a and ORF6 in viral pathogenesis, providing important information for the generation of attenuated forms of SARS-CoV-2 for their implementation as live attenuated vaccines for the treatment of SARS-CoV-2 infection and associated COVID-19. IMPORTANCE Despite great efforts put forward worldwide to combat the current coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a human health and socioeconomic threat. Insights into the pathogenesis of SARS-CoV-2 and the contribution of viral proteins to disease outcome remain elusive. Our study aims (i) to determine the contribution of SARS-CoV-2 accessory open reading frame (ORF) proteins to viral pathogenesis and disease outcome and (ii) to develop a synergistic platform combining our robust reverse-genetics system to generate recombinant SARS-CoV-2 constructs with a validated rodent model of infection and disease. We demonstrate that SARS-CoV-2 ORF3a and ORF6 contribute to lung pathology and ultimately disease outcome in K18 hACE2 transgenic mice, while ORF7a, ORF7b, and ORF8 have little impact on disease outcome. Moreover, our combinatory platform serves as a foundation for generating attenuated forms of the virus to develop live attenuated vaccines for the treatment of SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Open Reading Frames/immunology , SARS-CoV-2 , Viral Proteins , A549 Cells , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Chlorocebus aethiops , HEK293 Cells , Humans , Mice , Mice, Transgenic , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vero Cells , Viral Proteins/genetics , Viral Proteins/immunology
14.
Int J Mol Sci ; 21(21)2020 Nov 03.
Article in English | MEDLINE | ID: covidwho-1344351

ABSTRACT

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Subject(s)
Blood Platelets/pathology , Cardiovascular Diseases/virology , Coronavirus Infections/blood , Coronavirus Infections/pathology , Erythrocytes/pathology , Ferritins/blood , P-Selectin/blood , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Betacoronavirus/isolation & purification , Blood Coagulation/physiology , Blood Platelets/virology , COVID-19 , Cardiovascular Diseases/blood , Cardiovascular Diseases/pathology , Coronavirus Infections/virology , Erythrocytes/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Thrombosis/pathology , Thrombosis/virology
15.
J Med Internet Res ; 23(7): e27448, 2021 07 21.
Article in English | MEDLINE | ID: covidwho-1319560

ABSTRACT

BACKGROUND: The beginning of the COVID-19 pandemic presented many sudden challenges regarding food, including grocery shopping changes (eg, reduced store hours, capacity restrictions, and empty store shelves due to food hoarding), restaurant closures, the need to cook more at home, and closures of food access programs. Eat Well Saskatchewan (EWS) implemented a 16-week social media campaign, #eatwellcovid19, led by a dietitian and nutrition student that focused on sharing stories submitted by the Saskatchewan public about how they were eating healthy during the COVID-19 pandemic. OBJECTIVE: The goal of this study was to describe the implementation of the #eatwellcovid19 social media campaign and the results from the evaluation of the campaign, which included campaign performance using social media metrics and experiences and perspectives of campaign followers. METHODS: Residents of Saskatchewan, Canada, were invited to submit personal stories and experiences to EWS about how they were eating healthy during the COVID-19 pandemic from April to August 2020. Each week, one to three stories were featured on EWS social media platforms-Facebook, Instagram, and Twitter-along with evidence-based nutrition information to help residents become more resilient to challenges related to food and nutrition experienced during the COVID-19 pandemic. Individuals who submitted stories were entered into a weekly draw for a Can $100 grocery gift card. Social media metrics and semistructured qualitative interviews of campaign followers were used to evaluate the #eatwellcovid19 campaign. RESULTS: In total, 75 stories were submitted by 74 individuals on a variety of topics (eg, grocery shopping, traditional skills, and gardening), and 42 stories were featured on social media. EWS shared 194 #eatwellcovid19 posts across social media platforms (Facebook: n=100; Instagram: n=55; and Twitter: n=39). On Facebook, #eatawellcovid19 reached 100,571 followers and left 128,818 impressions, resulting in 9575 engagements. On Instagram, the campaign reached 11,310 followers, made 14,145 impressions, and received 823 likes and 15 comments. On Twitter, #eatwellcovid19 made 15,199 impressions and received 424 engagements. Featured story submission posts had the best engagement on Facebook and the most likes and comments on Instagram. The EWS social media pages reported increases in their following during the campaign (Instagram: +30%; Facebook: +14%; and Twitter: +12%). Results from the interviews revealed that there were two types of campaign followers: those who appreciated hearing the stories submitted by followers, as it helped them to feel connected to the community during social isolation, and those who appreciated the evidence-based information. CONCLUSIONS: Numerous stories were submitted to the #eatwellcovid19 social media campaign on various topics. On Instagram and Facebook, posts that featured these stories had the highest engagement. During this campaign, EWS's social media following increased by more than 10% on each platform. The approach used for the #eatwellcovid19 campaign could be considered by others looking to develop health promotion campaigns.


Subject(s)
COVID-19 , Diet, Healthy , Health Promotion/organization & administration , Health Promotion/statistics & numerical data , Pandemics , Qualitative Research , Social Media/statistics & numerical data , Adolescent , Adult , Aged , COVID-19/epidemiology , Emotions , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Saskatchewan/epidemiology , Young Adult
16.
Clin Dermatol ; 39(1): 33-40, 2021.
Article in English | MEDLINE | ID: covidwho-1300689

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has caused widespread disruptions in various sectors of medicine, including medical education. Although the necessary focus has been on patient care and public safety and the long-lasting impact of COVID-19 remains to be determined, the impact on medical education warrants further attention and action. While it seems minuscule compared with the toll the global pandemic has caused worldwide, the impact on medical education, including graduate medical education, carries the potential to alter career progression and outcomes. We have assessed the effects of COVID-19 on dermatology clinics, residency education, and medical education, exploring recommendations and actions taken by governing bodies and offering additional suggestions of our own.


Subject(s)
COVID-19/epidemiology , Certification , Dermatology/education , Internship and Residency , Skin Diseases , Accreditation , Biomedical Research , COVID-19/prevention & control , Curriculum , Humans , Internship and Residency/methods , Internship and Residency/organization & administration , Interviews as Topic , Personnel Selection , SARS-CoV-2 , Skin Diseases/diagnosis , Skin Diseases/pathology , Skin Diseases/therapy , Telemedicine , United States
17.
Int J Infect Dis ; 106: 323-328, 2021 May.
Article in English | MEDLINE | ID: covidwho-1279601

ABSTRACT

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has affected all healthcare systems. This study aimed to assess the impact of the COVID-19 pandemic on the number and severity of cases of community-acquired pneumonia (CAP) in Japan. METHODS: Using claims data from the Quality Indicator/Improvement Project (QIP) database, urgent cases of inpatients for CAP from 01 August 2018 to 30 July 2020 were included. The monthly ratios of inpatient cases were compared from August 2018 to July 2019 and August 2019 to July 2020 as a year-over-year comparison. These ratios were also compared according to the "A-DROP" severity score, and an interrupted time series (ITS) analysis was performed to evaluate the impact of the COVID-19 pandemic on the monthly number of inpatient cases. RESULTS: This study included a total of 67,900 inpatient cases for CAP in 262 hospitals. During the COVID-19 pandemic (defined as the period between March and July 2020) the number of inpatient cases for CAP drastically decreased compared with the same period in the previous year (-48.1%), despite a temporary reduction in the number of other urgent admissions. The number of inpatient cases decreased according to the severity of pneumonia. Milder cases showed a greater decrease in the year-over-year ratio than severe ones: mild -55.2%, moderate -45.8%, severe -39.4%, and extremely severe -33.2%. The ITS analysis showed that the COVID-19 pandemic significantly reduced the monthly number of inpatient cases for CAP (estimated decrease: -1233 cases; 95% CI -521 to -1955). CONCLUSIONS: This study showed a significant reduction in the number of inpatient cases for CAP during the COVID-19 pandemic in Japan. The milder cases showed a greater decrease in the year-over-year ratio of the number of inpatient cases.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/complications , Hospitalization , Pandemics/statistics & numerical data , Pneumonia/complications , Humans , Male
18.
Front Psychiatry ; 12: 645340, 2021.
Article in English | MEDLINE | ID: covidwho-1273363

ABSTRACT

Background: In this study, we aimed to explore the attitude of medical students toward their role and social accountability in this pandemic era. An online survey was developed to elicit information on (1) the role of medical students in the pandemic era; (2) Medical education in the "new normal," and (3) the impact of COVID-19 on medical students. Methods: The online survey, developed by a team consisting of three medical students, three psychiatry residents, and three professors of psychiatry, was conducted on 574 participants (213 medical students, 180 graduates, and 181 professors) in the University of Ulsan College of Medicine, Seoul, South Korea. Anxiety symptom rating scales, including the Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale and the Generalized Anxiety Disorder-7 (GAD-7) scale, were applied to measure participant anxiety level. Results: Medical students indicated their willingness to join the healthcare response to the COVID-19 pandemic, if requested; however, graduates and professors recommended that medical students continue their training rather than join the pandemic healthcare response. In the new normal era, medical education has had to change appropriately. Moreover, adequate knowledge of COVID-19 infection and spread must be considered for the continuation of clinical clerkships during the pandemic. Overall, medical students who indicated anxiety about treating possible or confirmed cases of COVID-19 rated higher on the SAVE-6 scale. Finally, medical students who reported that COVID-19 had an impact on their studies and daily life rated higher on the general anxiety scale (GAD-7). Conclusion: Social accountability is an important issue for medical students in the pandemic era. At the same time, non-disruption of their academic calendar would ensure continuous availability of component medical professionals, which is important for adequate future healthcare responses.

19.
Front Med (Lausanne) ; 8: 684032, 2021.
Article in English | MEDLINE | ID: covidwho-1273343

ABSTRACT

The COVID-19 pandemic has been a major burden for healthcare systems worldwide and has caused multiple changes and problems in outpatient care. The aim of this study was to investigate the impact of the COVID-19 pandemic on consultations and diagnoses in gastroenterology practices in Germany. To this end, we retrospectively analyzed data from the Disease Analyzer database (IQVIA) using the International Classification of Diseases, 10th revision (ICD-10). We included all patients aged ≥18 years with at least one visit to one of 48 gastroenterology practices in Germany between April and September 2019 and April and September 2020. A total of 63,914 patients in the 2nd quarter of 2019, 63,701 in the 3rd quarter of 2019, 55,769 in the 2nd quarter of 2020, and 60,446 in the 3rd quarter of 2020 were included. Overall, a clear downward trend in the number of visits to gastroenterologists was observed in the 2nd quarter of 2020 compared to 2019 (-13%, p = 0.228). The decrease in consultations was particularly pronounced in patients >70 years of age (-17%, p = 0.096). This trend was evident for all gastrointestinal diagnoses except for tumors. Most notably, rates of gastrointestinal infections (-19%) or ulcers (-43%) were significantly lower in this period than in the same quarter of 2019. Reflecting the course of the pandemic, the differences between the 3rd quarter of 2020 and that of 2019 were less pronounced (-5%, p = 0.560). Our data show that the pandemic changed patients' behavior with respect to the health care system. Using the example of German gastroenterology practices, we show that the number of consultations as well as the number and range of diagnoses have changed compared to the same period in 2019.

20.
World J Hepatol ; 13(5): 522-532, 2021 May 27.
Article in English | MEDLINE | ID: covidwho-1271018

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on public health and healthcare. The pandemic surge and resultant lockdown have affected the standard-of-care of many medical conditions and diseases. The initial uncertainty and fear of cross transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have changed the routine management of patients with pre-existing liver diseases, hepatocellular carcinoma, and patients either listed for or received a liver transplant. COVID-19 is best described as a multisystem disease caused by SARS-CoV-2, and it can cause acute liver injury or decompensation of the pre-existing liver disease. There has been considerable research on the pathophysiology, infection transmission, and treatment of COVID-19 in the last few months. The pathogenesis of liver involvement in COVID-19 includes viral cytotoxicity, the secondary effect of immune dysregulation, hypoxia resulting from respiratory failure, ischemic damage caused by vascular endotheliitis, congestion because of right heart failure, or drug-induced liver injury. Patients with chronic liver diseases, cirrhosis, and hepatocellular carcinoma are at high risk for severe COVID-19 and mortality. The phase III trials of recently approved vaccines for SARS-CoV-2 did not include enough patients with pre-existing liver diseases and excluded immunocompromised patients or those on immunomodulators. This article reviews the currently published research on the effect of COVID-19 on the liver and the management of patients with pre-existing liver disease, including SARS-CoV-2 vaccines.

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