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2.
J Med Virol ; 93(9): 5568-5573, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363700

ABSTRACT

Coronavirus disease 2019 (COVID-19) is one of the most pressing health problems of this century, but our knowledge of the disease is still limited. In this study, we aimed to examine serum-soluble urokinase plasminogen activator receptor (suPAR) and kidney injury molecule 1 (KIM-1) levels based on the clinical course of COVID-19. Our study included 102 patients over the age of 18 who were diagnosed as having COVID-19 between September 2020 and December 2020 and a control group of 50 health workers over the age of 18 whose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR results were negative. KIM-1 was measured by ELISA and suPAR by suPARnostic™ assay. Analysis of previously identified variables of prognostic significance in COVID-19 revealed high neutrophil to lymphocyte ratio, lactose dehydrogenase, prothrombin time, C-reactive protein, PaO2 /FiO2 , D-dimer, ferritin, and fibrinogen levels in patients with severe disease (p < 0.05 for all). KIM-1 and suPAR levels were significantly higher in COVID-19 patients compared to the control group (p = 0.001 for all). KIM-1 level was higher in severe patients compared to moderate patients (p = 0.001), while suPAR level was lower (p = 0.001). KIM-1, which is believed to play an important role in the endocytosis of SARS-CoV-2, was elevated in patients with severe COVID-19 and may be a therapeutic target in the future. SuPAR may have a role in defense mechanism and fibrinolysis, and low levels in severe patients may be associated with poor prognosis in the early period.


Subject(s)
COVID-19/blood , Hepatitis A Virus Cellular Receptor 1/blood , Receptors, Urokinase Plasminogen Activator/blood , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , COVID-19/diagnosis , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Severity of Illness Index
3.
Nat Med ; 27(3): 454-462, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319036

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Age of Onset , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/blood , Antibodies, Viral/analysis , Asymptomatic Infections , COVID-19/blood , COVID-19/pathology , Carrier State/blood , Carrier State/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunity/physiology , Immunoglobulin A/blood , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Young Adult
4.
J Reprod Immunol ; 146: 103344, 2021 08.
Article in English | MEDLINE | ID: covidwho-1315509

ABSTRACT

The pandemic COVID-19 presents a major challenge to identify effective drugs for treatment. Clinicians need evidence based on randomized trials regarding effective medical treatments for this infection. Currently no effective therapies exist for the progression of the mild forms to severe disease. Knowledge however is rapidly expanding. Remdesivir, an anti- retroviral agent has in vitro activity against this virus and has shown to decrease the duration of ICU care in patients with severe disease, while low dose dexamethasone also showed a decrease in the duration of stay in cases of severe disease requiring assisted ventilation. At the time of writing this article, two mRNA-based vaccines have shown an approximate 95 % efficacy in preventing infection in large clinical trials. At least one of these drugs has regulatory permission for vaccination in high-income countries. Low and middle-income countries may have difficulties in initiating vaccine programs on large scales because of availability, costs, refrigeration and dissemination. Adequately powered randomized trials are required for drugs with in vitro activity against the virus. Supportive care should be provided for stable, hypoxia and pneumonia free patients on imaging. Vaccines are of obvious benefit and given the preliminary evidence of the efficacy of over 95 %, Low and middle-income countries must develop links with the WHO COVAX program to ensure global distribution of vaccines.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/therapy , Evidence-Based Medicine/methods , Pandemics/prevention & control , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antimalarials/pharmacology , Antimalarials/therapeutic use , Antiviral Agents/pharmacology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/immunology , Clinical Trials as Topic , Evidence-Based Medicine/trends , Global Health , Humans , International Cooperation , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spike Glycoprotein, Coronavirus/metabolism , Treatment Outcome , Virus Internalization/drug effects
5.
Bull World Health Organ ; 99(1): 62-66, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1304565

ABSTRACT

PROBLEM: The surge in coronavirus disease 2019 (COVID-19) cases overwhelmed the health system in the Republic of Korea. APPROACH: To help health-care workers prioritize treatment for patients with more severe disease and to decrease the burden on health systems caused by COVID-19, the government established a system to classify disease severity. Health-care staff in city- and provincial-level patient management teams classified the patients into the different categories according to the patients' pulse, systolic blood pressure, respiratory rate, body temperature and level of consciousness. Patients categorized as having moderate, severe and very severe disease were promptly assigned to beds or negative-pressure isolation rooms for hospital treatment, while patients with mild symptoms were monitored in 16 designated facilities across the country. LOCAL SETTING: The case fatality rate was higher in the city of Daegu and the Gyeongsangbuk-do province (1.6%; 124/7756) than the rest of the country (0.5%; 7/1485). RELEVANT CHANGES: From 25 February to 26 March 2020, the ratio of negative-pressure isolation rooms per COVID-19 patient was below 0.15 in the city of Daegu and the Gyeongsangbuk-do province. In the rest of the country, this ratio decreased from 5.56 to 0.63 during the same period. Before the classification system was in place, eight (15.7%) out of the 51 deaths occurred at home or during transfer from home to health-care institutions. LESSONS LEARNT: Categorizing patients according to their disease severity should be a prioritized measure to ease the burden on health systems and reduce the case fatality rate.


Subject(s)
COVID-19/classification , COVID-19/epidemiology , Severity of Illness Index , Humans , Pandemics , Patient Isolation , Pneumonia, Viral/epidemiology , Republic of Korea/epidemiology , SARS-CoV-2 , Vital Signs
6.
Immunology ; 164(1): 135-147, 2021 09.
Article in English | MEDLINE | ID: covidwho-1295026

ABSTRACT

Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Saliva
7.
Indian J Ophthalmol ; 69(7): 1909-1914, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278602

ABSTRACT

Purpose: To report endogenous fungal endophthalmitis, postrecovery from severe COVID-19 infection in otherwise immunocompetent individuals, treated with prolonged systemic steroids. Methods: Retrospective chart review of cases with confirmed and presumed fungal endogenous endophthalmitis, following severe COVID-19 disease, treated at two tertiary care referral eye institutes in North India. Results: Seven eyes of five cases of endogenous fungal endophthalmitis were studied. All cases had been hospitalized for severe COVID-19 pneumonia and had received systemic steroid therapy for an average duration of 42 ± 25.1 days (range 18-80 days). All the cases initially complained of floaters with blurred vision after an average of 6 days (range 1-14 days) following discharge from hospital. They had all been misdiagnosed as noninfectious uveitis by their primary ophthalmologists. All eyes underwent pars plana vitrectomy (PPV) with intravitreal antifungal therapy. Five of the seven eyes grew fungus as the causative organism (Candida sp. in four eyes, Aspergillus sp. in one eye). Postoperatively, all eyes showed control of the infection with a marked reduction in vitreous exudates and improvement in vision. Conclusion: Floaters and blurred vision developed in patients after they recovered from severe COVID-19 infection. They had received prolonged corticosteroid treatment for COVID-19 as well as for suspected noninfectious uveitis. We diagnosed and treated them for endogenous fungal endophthalmitis. All eyes showed anatomical and functional improvement after PPV with antifungal therapy. It is important for ophthalmologists and physicians to be aware of this as prompt treatment could control the infection and salvage vision.


Subject(s)
COVID-19 , Endophthalmitis , Eye Infections, Fungal , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Endophthalmitis/etiology , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/surgery , Fungi , Humans , India/epidemiology , Retrospective Studies , SARS-CoV-2 , Visual Acuity , Vitrectomy
8.
Crit Care Explor ; 3(6): e0441, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1262253

ABSTRACT

OBJECTIVES: To evaluate factors predictive of clinical progression among coronavirus disease 2019 patients following admission, and whether continuous, automated assessments of patient status may contribute to optimal monitoring and management. DESIGN: Retrospective cohort for algorithm training, testing, and validation. SETTING: Eight hospitals across two geographically distinct regions. PATIENTS: Two-thousand fifteen hospitalized coronavirus disease 2019-positive patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anticipating Respiratory failure in Coronavirus disease (ARC), a clinically interpretable, continuously monitoring prognostic model of acute respiratory failure in hospitalized coronavirus disease 2019 patients, was developed and validated. An analysis of the most important clinical predictors aligns with key risk factors identified by other investigators but contributes new insights regarding the time at which key factors first begin to exhibit aberrency and distinguishes features predictive of acute respiratory failure in coronavirus disease 2019 versus pneumonia caused by other types of infection. Departing from prior work, ARC was designed to update continuously over time as new observations (vitals and laboratory test results) are recorded in the electronic health record. Validation against data from two geographically distinct health systems showed that the proposed model achieved 75% specificity and 77% sensitivity and predicted acute respiratory failure at a median time of 32 hours prior to onset. Over 80% of true-positive alerts occurred in non-ICU settings. CONCLUSIONS: Patients admitted to non-ICU environments with coronavirus disease 2019 are at ongoing risk of clinical progression to severe disease, yet it is challenging to anticipate which patients will develop acute respiratory failure. A continuously monitoring prognostic model has potential to facilitate anticipatory rather than reactive approaches to escalation of care (e.g., earlier initiation of treatments for severe disease or structured monitoring and therapeutic interventions for high-risk patients).

9.
Cardiovasc Endocrinol Metab ; 10(2): 80-88, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1254955

ABSTRACT

The adaptive use of Janus kinase (JAK)-inhibitors has been suggested by rheumatology experts in the management of COVID-19. We recount the rationale behind their use in this setting, and the current evidence for and against their use in this review. JAK-inhibitors role in COVID-19 infection appears to be multifaceted, including preventing viral endocytosis and dampening the effect of excessive chemokines. This drug class may be able to achieve these effects at already preapproved dosages. Concerns arise regarding reactivation of latent viral infections and the feasibility of their use in those with severe disease. Most interestingly, JAK-Inhibitors may also have an additional advantage for diabetic and obese populations, where the dysregulation of JAK-signal transducer and activator of transcription pathway may be responsible for their increased risk of poor outcomes. Targeting this pathway may provide a therapeutic advantage for these patient groups.

10.
Pediatr Pulmonol ; 56(8): 2522-2529, 2021 08.
Article in English | MEDLINE | ID: covidwho-1248712

ABSTRACT

BACKGROUND: Initially, persistent asthma was deemed a risk factor for severe COVID-19 disease. However, data suggests that asthmatics do not have an increased risk of COVID-19 infection or disease. There is a paucity of data describing pediatric asthmatics with COVID-19. OBJECTIVE: The objectives of this study were to determine the prevalence of asthma among hospitalized children with acute symptomatic COVID-19, compare demographic and clinical outcomes between asthmatics and nonasthmatics, and characterize behaviors of our outpatient pediatric population. METHODS: We conducted a single-center retrospective study of pediatric patients admitted to the Cohen Children's Medical Center at Northwell Health with symptomatic COVID-19 within 4 months of the surge beginning in March 2020 and a retrospective analysis of pediatric asthma outpatients seen in the previous 6 months. Baseline demographic variables and clinical outcomes for inpatients, and medication compliance, health behaviors, and asthma control for outpatients were collected. RESULTS: Thirty-eight inpatients and 95 outpatients were included. The inpatient prevalence of asthma was 34.2%. Asthmatics were less likely to have abnormal chest x-rays (CXRs), require oxygen support, and be treated with remdesivir. Among outpatients, 41% reported improved asthma control and decreased rescue medication use, with no COVID-19 hospitalizations, despite six suspected infections. CONCLUSIONS: Among children hospitalized for acute symptomatic COVID-19 at our institution, 34.2% had a diagnosis of asthma. Asthmatics did not have a more severe course and required a lower level of care. Outpatients had improved medication compliance and control and a low risk of hospitalization. Biological and behavioral factors may have mitigated against severe disease.


Subject(s)
Asthma , COVID-19 , Adolescent , Asthma/drug therapy , Asthma/epidemiology , Child , Female , Hospitalization , Hospitals, Pediatric , Humans , Inpatients , Male , Outpatients , Retrospective Studies , SARS-CoV-2
11.
J Clin Invest ; 131(14)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1249496

ABSTRACT

The SARS-CoV-2 virus, which causes COVID-19, has been associated globally with substantial morbidity and mortality. Numerous reports over the past year have described the clinical and immunological profiles of COVID-19 patients, and while some trends have emerged for risk stratification, they do not provide a complete picture. Therefore, efforts are ongoing to identify genetic susceptibility factors of severe disease. In this issue of the JCI, Povysil et al. performed a large, multiple-country study, sequencing genomes from patients with mild and severe COVID-19, along with population controls. Contrary to previous reports, the authors observed no enrichment of predicted loss-of-function variants in genes in the type I interferon pathway, which might predispose to severe disease. These studies suggest that more evidence is needed to substantiate the hypothesis for a genetic immune predisposition to severe COVID-19, and highlights the importance of considering experimental design when implicating a monogenic basis for severe disease.


Subject(s)
COVID-19 , Interferon Type I , Genetic Predisposition to Disease , Humans , SARS-CoV-2
12.
Expert Rev Respir Med ; 15(10): 1303-1316, 2021 10.
Article in English | MEDLINE | ID: covidwho-1246642

ABSTRACT

Introduction: Severe asthma and chronic rhinosinusitis (CRS), with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), are heterogeneous diseases characterized by different mechanistic pathways (endotypes) and variable clinical presentations (phenotypes).Areas covered: This review provides the clinician with an overview of the prevalence and clinical impact of severe chronic upper and lower airways disease and suggests a novel therapeutic approach with biological agents with possible biomarkers. To select relevant literature for inclusion in this review, we conducted a literature search using the PubMed database, using terms 'severe airways disease' AND 'endotype' AND 'treatment.' The literature review was performed for publication years 2010-2020, restricting the articles to humans and English language publications.Expert opinion: The coronavirus disease (COVID-19) pandemic has brought forth many challenges for patients with severe airway disease and healthcare practitioners involved in care. These patients could have an increased risk of developing severe SARS-CoV-2 disease, although treatment with biologics is not associated with a worse prognosis. Eosinopenia on hospital admission plays a key role as a diagnostic and prognostic biomarker.


Subject(s)
COVID-19 , Nasal Polyps , Rhinitis , Sinusitis , Chronic Disease , Humans , SARS-CoV-2
13.
Bone Marrow Transplant ; 56(7): 1493-1508, 2021 07.
Article in English | MEDLINE | ID: covidwho-1241800

ABSTRACT

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an "endemic" phase and therefore an ongoing risk within a "new normality". These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.


Subject(s)
Autoimmune Diseases , COVID-19 , Hematopoietic Stem Cell Transplantation , Adult , Autoimmune Diseases/therapy , Child , Humans , Pandemics , SARS-CoV-2
14.
Lancet Reg Health Eur ; 5: 100118, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1230649
15.
Ther Adv Infect Dis ; 8: 20499361211009380, 2021.
Article in English | MEDLINE | ID: covidwho-1226855

ABSTRACT

Diabetes mellitus (DM) is an important risk factor for both severe disease and death due to coronavirus-2019 (COVID-19). About 19 million of the 463 million persons living with DM (PLWD) globally are found in sub-Saharan Africa (SSA). The dual burden of DM and poverty in SSA, coupled with the rising number of cases of COVID-19 in this region, predisposes PLWD to inadequate care and poor glycemic controls due to the disruption to the economy and the healthcare system. The risk of acquisition of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among PLWD is the same as those in the general population. Therefore, the standard preventive measures outlined by the World Health Organization must be strictly adhered to. In addition, maintaining adequate glycemic control is associated with better outcomes in DM patients with COVID-19. In SSA, adequate supply of DM medication while patients stay at home is crucial to minimize routine hospital visits since DM clinics are usually overcrowded and have longer waiting times, which may maximize risk of SARS-CoV-2 transmission to PLWD across the region. Psychosocial support to improve adherence to anti-hyperglycemic medications may improve COVID-19 outcomes. Trained healthcare professionals should diagnose and evaluate severity comprehensively as well as evaluate the need for in-patient care for PLWD with COVID-19 irrespective of disease severity. Due to the increased risk of severe disease, a multi-disciplinary approach to the management of COVID-19 in PLWD should preferably be in a setting where close monitoring is available, typically a health facility, even for mild disease that may require home management according to local guidelines. In conclusion, DM complicates COVID-19 outcomes and the on-going COVID-19 pandemic adversely affects DM care at individual and global public health levels. PLWD should be prioritized as COVID-19 vaccines are being rolled out.

16.
Sci Rep ; 11(1): 9927, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225516

ABSTRACT

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22-2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.


Subject(s)
COVID-19/therapy , Adult , Aged , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Female , Ferritins/metabolism , Humans , Immunization, Passive , Male , Middle Aged , Pilot Projects , Prospective Studies , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Rate , Treatment Outcome
17.
J Gen Virol ; 102(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1219293

ABSTRACT

SARS-CoV-2 is the causative agent of COVID-19 and human infections have resulted in a global health emergency. Small animal models that reproduce key elements of SARS-CoV-2 human infections are needed to rigorously screen candidate drugs to mitigate severe disease and prevent the spread of SARS-CoV-2. We and others have reported that transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) viral receptor under the control of the Keratin 18 (K18) promoter develop severe and lethal respiratory disease subsequent to SARS-CoV-2 intranasal challenge. Here we report that some infected mice that survive challenge have residual pulmonary damages and persistent brain infection on day 28 post-infection despite the presence of anti-SARS-COV-2 neutralizing antibodies. Because of the hypersensitivity of K18-hACE2 mice to SARS-CoV-2 and the propensity of virus to infect the brain, we sought to determine if anti-infective biologics could protect against disease in this model system. We demonstrate that anti-SARS-CoV-2 human convalescent plasma protects K18-hACE2 against severe disease. All control mice succumbed to disease by day 7; however, all treated mice survived infection without observable signs of disease. In marked contrast to control mice, viral antigen and lesions were reduced or absent from lungs and absent in brains of antibody-treated mice. Our findings support the use of K18-hACE2 mice for protective efficacy studies of anti-SARS-CoV-2 medical countermeasures (MCMs). They also support the use of this system to study SARS-CoV-2 persistence and host recovery.


Subject(s)
COVID-19/therapy , Acute Lung Injury/prevention & control , Acute Lung Injury/virology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Brain/pathology , Brain/virology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Disease Models, Animal , Female , Humans , Immunization, Passive , Lung/pathology , Lung/virology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Coronavirus/genetics , Receptors, Coronavirus/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load , Virus Replication
18.
Int Heart J ; 62(3): 540-545, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1216967

ABSTRACT

This study aims to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on patient admissions to Hunan's cardiac intensive care units (CCUs).We conducted a retrospective, single-center study. Data were collected from patients who were confirmed to have critical cardiovascular disease and admitted to the CCU of the Second Xiangya Hospital of Central South University, Hunan, from January 23 to April 23, 2020. Compared with the same period in 2019, the results show that the number of hospitalization decreased by 19.6%; the inhospital mortality rate of CCU was decreased (28.57% versus 16.67%; odds ratio (OR), 0.50; 95% confidence interval (CI), 0.251-0.996; P = 0.047); hospital stay was decreased (7.97 versus 12.36, P < 0.001); hospital emergency percutaneous coronary intervention (PCI) rate in patients with acute coronary syndromes (ACS) significantly decreased (76.00% versus 39.00%, P < 0.001); among this, the PCI rate of patients with ST-segment elevation myocardial infarction (STEMI) decreased (76.32% versus 55.17%, P = 0.028) as well. In addition, the number of patients transferred from other hospitals significantly decreased (76.79% versus 56.67%, P = 0.002), and the number of patients transferred from other cities also decreased by 10.75%.During the outbreak of the COVID-19 epidemic in Hunan Province, the number of patients admitted to CCU decreased, as well as the mortality rate; fewer patients with severe cardiovascular disease can be transported to better hospitals from remote rural areas. In addition to epidemic prevention and control, experts in China should focus on improved emergency transport medical services to reduce this impact.


Subject(s)
COVID-19 , Cardiovascular Diseases/mortality , Coronary Care Units/trends , Hospital Mortality/trends , Patient Admission/trends , Patient Transfer/trends , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/prevention & control , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/therapy , China/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies
19.
Pediatr Rheumatol Online J ; 19(1): 68, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1216904

ABSTRACT

BACKGROUND: SARS-CoV-2 can induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators (cytokine storm), strongly contributing to the pulmonary and systemic manifestations in severe coronavirus disease 2019 (COVID-19). As a consequence, different drugs active on the immune system have been proposed for the treatment of the disease in adults. ROLE OF THE ANTI-RHEUMATIC AGENTS IN CHILDREN: Children are more likely to develop a mild disease course, as the severe form of COVID-19 is identified in less than 5% of the pediatric patients. Moreover, in children a peculiar disease phenotype, defined as multisystem inflammatory syndrome in children (MIS-C) is observed, representing the most severe expression of the inflammatory dysregulation caused by SARS-CoV-2. The limited experience with the severe pediatric COVID-19 and MIS-C does not allow conclusions about the role of the immune pharmacological approach, and therefore the treatment of these conditions represents a considerable clinical challenge. The use of chloroquine, hydroxychloroquine, and colchicine in the early disease stages is not sufficiently supported by evidence, and there is an increasing interest in the role of biologic agents, including anti-IL-1 and anti-IL-6 agents, in the prevention and treatment of the severe manifestations of COVID-19. CONCLUSION: The therapeutic approach to pediatric COVID-19 is multidisciplinary, and anti-rheumatic agents have a prominent role in severe disease. This paper reviews the rationale for the use of anti-rheumatic agents in pediatric COVID-19 and MIS-C and the clinical experience with the single drugs. Finally, the areas of potential improvement in the use of anti-rheumatic agents, including the optimization of the drug choice and the timing of administration, are discussed.


Subject(s)
Antirheumatic Agents/pharmacology , Biological Factors/pharmacology , COVID-19 , Systemic Inflammatory Response Syndrome , COVID-19/complications , COVID-19/drug therapy , COVID-19/immunology , COVID-19/prevention & control , Child , Humans , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/prevention & control , Treatment Outcome
20.
Front Immunol ; 12: 665522, 2021.
Article in English | MEDLINE | ID: covidwho-1211818

ABSTRACT

COVID-19 is characterized by a severe pulmonary disease due to severe acute respiratory syndrome (SARS)-CoV-2 infection. For clinicians involved in the management of patients with chronic autoimmune diseases the risk linked to the conditions itself and to drug-induced immunosuppression during the COVID-19 pandemic is a major topic. Pemphigus is a rare autoimmune blistering disease (AIBD) of the skin and mucous membranes caused by autoantibodies to desmosomal components, desmoglein 1 and 3. Among immunosuppressant therapies, rituximab (RTX) is considered a highly effective treatment with a favorable safety profile, but it induces a prolonged B-cell depletion that can lead to higher susceptibility to infections. For this reason, concerns about its use during the pandemic have been raised. We describe a case of a pemphigus patient in which RTX-induced B cell depletion led to the severe inflammatory phase, whereas corticosteroid treatment allowed a favorable outcome.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , B-Lymphocytes/immunology , COVID-19/drug therapy , Pemphigus/immunology , Rituximab/adverse effects , Adrenal Cortex Hormones/adverse effects , B-Lymphocytes/metabolism , COVID-19/complications , COVID-19/physiopathology , Female , Fever , Humans , Immunoglobulin G/immunology , Inflammation/drug therapy , Middle Aged , Oxygen Inhalation Therapy , Pemphigus/complications , Pemphigus/drug therapy , Rituximab/therapeutic use
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