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1.
Medicine (Baltimore) ; 99(33): e21520, 2020 Aug 14.
Article in English | MEDLINE | ID: covidwho-740194

ABSTRACT

RATIONALE: Information regarding the clinical features and outcomes of pneumonia due to an infection with human coronavirus (HCoV)-OC43 in children with cancer is rare. This report presents the clinical features in terms of chest CT scan images which may be used to identify cases of HCoV-OC43 infection induced pneumonia in immunocompromised children. PATIENT CONCERNS: We report here a girl with acute lymphoblastic leukemia who developed respiratory symptoms during febrile neutropenia. Rapid clinical progression and nodular lesions on her chest X-ray and computed tomography scans were suggestive of a pulmonary fungal infection. DIAGNOSIS: A series of tests eventually confirmed the exclusive presence of HCoV-OC43 by the FilmArray Respiratory Panel from a throat swab sample. INTERVENTIONS: After the diagnosis was confirmed, the antimicrobial agents initially administered were discontinued. OUTCOMES: Although the chest CT scan images looked severe, the clinical course of the infection induced pneumonia was benign. The respiratory status of the patient was completely resolved in 2 weeks. LESSONS: This report highlights the importance of early identification of respiratory viruses, via the realization of their clinical characteristics, which helps reduce the duration of administration of antimicrobial agents in this setting.


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Child , Coronavirus Infections/complications , Coronavirus OC43, Human/isolation & purification , Febrile Neutropenia/complications , Female , Humans , Immunocompromised Host , Pneumonia, Viral/complications , Polymerase Chain Reaction
2.
Viruses ; 12(9)2020 08 23.
Article in English | MEDLINE | ID: covidwho-727450

ABSTRACT

RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19).


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , RNA Interference , Animals , Antiviral Agents/therapeutic use , Computational Biology , Gene Silencing , Humans , Immunocompromised Host , Pandemics
3.
Am J Case Rep ; 21: e926464, 2020 Aug 16.
Article in English | MEDLINE | ID: covidwho-721634

ABSTRACT

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.


Subject(s)
Acute Kidney Injury/chemically induced , Coronavirus Infections/complications , Gram-Negative Bacterial Infections/complications , Pneumonia, Bacterial/microbiology , Pneumonia, Viral/complications , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Betacoronavirus , Clinical Deterioration , Coinfection , Coronavirus Infections/drug therapy , Fatal Outcome , Humans , Immunocompromised Host , Kidney Transplantation , Male , Middle Aged , Pandemics , Pneumonia, Bacterial/drug therapy , Pneumonia, Viral/drug therapy , Stenotrophomonas maltophilia , Transplant Recipients , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
4.
Pan Afr Med J ; 36: 81, 2020.
Article in English | MEDLINE | ID: covidwho-709537

ABSTRACT

Sickle cell disease is a major concern of public health significance in Africa. Nearly 2/3rd of the global burden of sickle cell disease (SCD) is found to be in sub-Saharan Africa. There is increased mortality risk in sickle cell disease patients in Africa due to associated complications such as acute chest syndrome, asthma, pulmonary emboli and sepsis. Sickle cell disease management is the major contributor of financial burden on the government. Moreover, there is a shortage of medical specialists in Africa. COVID-19 pandemic has further led to devastating impact on economy and health globally. The chances of SCD patient contracting COVID-19 infections are higher as these patients are immunocompromised and may be at a higher risk of mortality. Practicing preventive measures including isolation and social distancing by these patients will prevent mortality rates as well as economic burden on government in the present unprecedented COVID-19 pandemic.


Subject(s)
Anemia, Sickle Cell/epidemiology , Coronavirus Infections/epidemiology , Cost of Illness , Pneumonia, Viral/epidemiology , Africa South of the Sahara/epidemiology , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/mortality , Coronavirus Infections/economics , Coronavirus Infections/prevention & control , Humans , Immunocompromised Host , Pandemics/economics , Pandemics/prevention & control , Pneumonia, Viral/economics , Pneumonia, Viral/prevention & control , Public Health , Social Isolation
5.
J Immunother Cancer ; 8(2)2020 07.
Article in English | MEDLINE | ID: covidwho-691258

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on immunocompromised CAR T-cell therapy recipients and kidney transplant recipients (KTRs) has not yet been established. CASE PRESENTATION: In this report, we compare two patients with severe COVID-19 pneumonia in either the humoral or cell-mediated immunodeficient states. The first patient was a man in his early 30s who was diagnosed with refractory multiple myeloma. He received fully humanized, anti-B-cell maturation antigen, CAR T-cell therapy before 4 months and achieved strict complete remission. He was infected with SARS-CoV-2 starting on January 26, 2019 and gradually progressed to severe pneumonia. Throughout the clinical progression of the disease, SARS-CoV-2 could not be cleared due to his humoral immunodeficient state. During this period of his severe COVID-19 pneumonia, elevated cytotoxic T-cells were observed in this patient's peripheral blood while elevated plasma levels of interleukin (IL)-2R, IL-6, tumor necrosis factor α, and ferritin were observed in his cytokine profiles. This patient eventually progressed into acute respiratory distress syndrome and recieved non-invasive ventilatory support. He failed to generate specific SARS-CoV-2 antibodies and died of respiratory failure on day 33 (d33). The second patient was a 52-year-old kidney transplant recipient (KTR) who took ciclosporin after renal transplantation for more than 7 years. He confirmed SARS-CoV-2 infection on January 20, 2019 and gradually progressed into severe pneumonia on d16 with a slightly elevated B-cell percentage and normal T-lymphocyte subsets. Viral clearance occurred together with the generation of specific anti-immunoglobulin G-SARS-CoV-2 antibodies after 2 weeks of treatment. He was symptom-free and discharged from the hospital on d42. CONCLUSION: We report a CAR T-cell therapy recipient diagnosed with COVID-19 for the first time. His virus clearance failure and life-threating cytokine storm during SARS-CoV-2 infection suggested that any decision to proceed CAR T-cell therapy during COVID-19 pandemics will require extensive discussion of potential risks and benefits. Immunosuppressant treatment based on ciclosporin could be relatively safe for KTRs diagnosed with COVID-19. TRIAL REGISTRATION NUMBER: ChiCTR-OPN-1800018137.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunocompromised Host , Pneumonia, Viral/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Antibodies, Viral/metabolism , Cyclosporine/therapeutic use , Cytokines/metabolism , Fatal Outcome , Humans , Immunity, Cellular , Immunity, Humoral , Male , Middle Aged , Pandemics
6.
Front Immunol ; 11: 1548, 2020.
Article in English | MEDLINE | ID: covidwho-687591

ABSTRACT

Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Diabetes Mellitus/epidemiology , Dietary Supplements , Neoplasms/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Renal Insufficiency, Chronic/epidemiology , Actinobacteria/chemistry , Biomarkers/blood , Cardiovascular Diseases/immunology , Comorbidity , Coronavirus Infections/diet therapy , Coronavirus Infections/mortality , Cytokines/blood , Diabetes Mellitus/immunology , Humans , Immunocompromised Host , Neoplasms/immunology , Pandemics , Pneumonia, Viral/diet therapy , Pneumonia, Viral/mortality , Renal Insufficiency, Chronic/immunology , beta-Glucans/pharmacology , beta-Glucans/therapeutic use
7.
Front Immunol ; 11: 1648, 2020.
Article in English | MEDLINE | ID: covidwho-685338

ABSTRACT

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Critical Care/methods , Cytokines/blood , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Clinical Decision-Making/methods , Coronavirus Infections/blood , Coronavirus Infections/mortality , Critical Illness , Endothelial Cells/metabolism , Female , Humans , Immunocompromised Host , Interleukin-6/antagonists & inhibitors , Janus Kinase Inhibitors/therapeutic use , Male , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Sex Factors , Thrombosis
8.
Neurologia ; 35(6): 357-362, 2020.
Article in English, Spanish | MEDLINE | ID: covidwho-680554

ABSTRACT

INTRODUCTION: The COVID-19 pandemic is changing approaches to diagnosis, treatment, and care provision in multiple sclerosis (MS). During both the initial and peak phases of the epidemic, the administration of disease-modifying drugs, typically immunosuppressants administered in pulses, was suspended due to the uncertainty about their impact on SARS-CoV-2 infection, mainly in contagious asymptomatic/presymptomatic patients. The purpose of this study is to present a safety algorithm enabling patients to resume pulse immunosuppressive therapy (PIT) during the easing of lockdown measures. METHODS: We developed a safety algorithm based on our clinical experience with MS and the available published evidence; the algorithm assists in the detection of contagious asymptomatic/presymptomatic cases and of patients with mild symptoms of SARS-CoV-2 infection with a view to withdrawing PIT in these patients and preventing new infections at day hospitals. RESULTS: We developed a clinical/microbiological screening algorithm consisting of a symptom checklist, applied during a teleconsultation 48hours before the scheduled session of PIT, and PCR testing for SARS-CoV-2 in nasopharyngeal exudate 24hours before the procedure. CONCLUSION: The application of our safety algorithm presents a favourable risk-benefit ratio despite the fact that the actual proportion of asymptomatic and presymptomatic individuals is unknown. Systematic PCR testing, which provides the highest sensitivity for detecting presymptomatic cases, combined with early detection of symptoms of SARS-CoV-2 infection may reduce infections and improve detection of high-risk patients before they receive PIT.


Subject(s)
Algorithms , Betacoronavirus/isolation & purification , Coronavirus Infections/prevention & control , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis/drug therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Ambulatory Care , Asymptomatic Diseases , Checklist , Clinical Laboratory Techniques , Contraindications, Drug , Coronavirus Infections/diagnosis , Disease Susceptibility , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Mass Screening/methods , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Polymerase Chain Reaction , Pulse Therapy, Drug , Quarantine , Risk Assessment , Symptom Assessment , Telemedicine
9.
AIDS Res Ther ; 17(1): 46, 2020 07 23.
Article in English | MEDLINE | ID: covidwho-671088

ABSTRACT

BACKGROUND: The COVID-19 has been a severe pandemic all around the world. Nowadays the patient with co-infection of HIV and SARS-CoV-2 was rarely reported. Here we reported a special case with HIV and SARS-CoV-2 co-infection, which showed a prolonged viral shedding duration. CASE PRESENTATION: The patient was infected with HIV 8 years ago through sexual transmission and had the normal CD4+T cell count. She was found SARS-CoV-2 positive using real-time Polymerase Chain Reaction (RT-PCR) during the epidemic. Most importantly, the patient had a prolonged viral shedding duration of SARS-CoV-2 about 28 days. CONCLUSION: The viral shedding duration may be prolonged in people living with HIV. The 14 days isolation strategy might not be long enough for them. The isolation or discharge of these patients needs further confirmation for preventing epidemics.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , HIV Infections/complications , Pneumonia, Viral/diagnosis , Virus Shedding , Benzoxazines/administration & dosage , Betacoronavirus/genetics , Betacoronavirus/immunology , C-Reactive Protein/analysis , CD4 Lymphocyte Count , Chills , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Fatigue , Female , Fever , HIV/growth & development , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Immunocompromised Host , Immunoglobulin M/blood , Lamivudine/administration & dosage , Middle Aged , Pandemics , Pharyngitis , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/drug therapy , Real-Time Polymerase Chain Reaction , Sputum/virology , Time Factors , Tomography, X-Ray Computed , Virus Shedding/immunology , Zidovudine/administration & dosage
10.
Int J Oncol ; 57(2): 533-539, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-667782

ABSTRACT

Severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV2) is the cause of a new disease (COVID­19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID­19. SARS­CoV­2 infection of host cells is facilitated by the angiotensin­converting enzyme 2 (ACE­2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE­2, a systematic analysis of these two other SARS­CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B­cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo­methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan­cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.


Subject(s)
Betacoronavirus/pathogenicity , Biomarkers, Tumor/genetics , Cathepsin L/genetics , Coronavirus Infections/virology , Neoplasms/genetics , Opportunistic Infections/virology , Pneumonia, Viral/virology , Serine Endopeptidases/genetics , Virus Internalization , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , DNA Methylation , Databases, Genetic , Female , Host-Pathogen Interactions , Humans , Immunocompromised Host , Male , Neoplasms/enzymology , Neoplasms/immunology , Opportunistic Infections/enzymology , Opportunistic Infections/immunology , Pandemics , Pneumonia, Viral/enzymology , Pneumonia, Viral/immunology , Risk Factors
11.
J Infect Dis ; 222(7): 1103-1107, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-663915

ABSTRACT

The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/virology , Fever/drug therapy , Fever/virology , Humans , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/virology , Time Factors , Treatment Outcome
12.
Gastroenterol Hepatol ; 43(6): 332-347, 2020.
Article in English, Spanish | MEDLINE | ID: covidwho-658769

ABSTRACT

The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: (a)To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. (b)To protect all healthcare professionals against the risks of infection with SARS-CoV-2. (c)To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.


Subject(s)
Coronavirus Infections/prevention & control , Gastroenterology/organization & administration , Hospital Departments/organization & administration , Infection Control/organization & administration , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Appointments and Schedules , Clinical Laboratory Techniques , Clinical Trials as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Cross Infection/prevention & control , Diagnostic Techniques, Digestive System/instrumentation , Digestive System Diseases/complications , Digestive System Diseases/diagnosis , Digestive System Diseases/therapy , Disinfection , Drug Interactions , Equipment Contamination/prevention & control , Home Care Services/organization & administration , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Liver Transplantation , Mass Screening/organization & administration , Occupational Diseases/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/transmission , Protective Devices , Symptom Assessment , Telemedicine/organization & administration , Universal Precautions
13.
J Hematol Oncol ; 13(1): 94, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-647080

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York. METHODS: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. RESULTS: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19-68) days from initial positive PCR. CONCLUSIONS: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Multiple Myeloma/complications , Pneumonia, Viral/complications , Tertiary Care Centers , Agammaglobulinemia/mortality , Agammaglobulinemia/pathology , Aged , Cohort Studies , Coronavirus Infections/mortality , Female , Humans , Immunocompromised Host , Inflammation/mortality , Inflammation/pathology , Male , Middle Aged , Multiple Myeloma/immunology , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , Risk Factors
14.
Subst Use Misuse ; 55(11): 1900-1901, 2020.
Article in English | MEDLINE | ID: covidwho-643514

ABSTRACT

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.


Subject(s)
Analgesics, Opioid/adverse effects , Arrhythmias, Cardiac/chemically induced , Coronavirus Infections/complications , Immunocompromised Host/immunology , Opioid-Related Disorders/complications , Pneumonia, Viral/complications , Respiratory Insufficiency/chemically induced , Adaptive Immunity/immunology , Analgesics, Opioid/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Drug Interactions , Humans , Immunity, Innate/immunology , Methadone/adverse effects , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Prognosis , Respiratory Insufficiency/physiopathology
15.
Curr Opin Infect Dis ; 33(4): 304-311, 2020 08.
Article in English | MEDLINE | ID: covidwho-643197

ABSTRACT

PURPOSE OF THE REVIEW: Laboratory-developed tests (LDTs) are essential for the clinical care of immunocompromised individuals. These patients often require specialized testing not available from commercial manufacturers and are therefore dependent on the laboratory to create, validate, and perform these assays. Recent paradigm-shifting legislation could alter the way that LDTs are operationalized and regulated. RECENT FINDINGS: On March 5th, 2020 the Verifying Accurate and Leading-Edge In-Vitro Clinical Tests Development Act (VALID) was introduced in the US Congress. This statute would overhaul existing regulatory framework by unifying the oversight of LDTs and commercial in-vitro diagnostic tests (IVDs) through the FDA. If enacted, LDTs would be subject to regulatory requirements like those found in commercial submissions for market review. Stakeholders continue to discuss the details and scope of the proposed legislation in the setting of the Severe Acute Respiratory Syndrome Coronavirus 2 pandemic, where LDTs are integral to the national COVID-19 response. SUMMARY: Congressional lawmakers have introduced legislation to alter the regulatory framework governing LDTs. Moving forward, a balance must be struck to ensure the availability of safe and accurate testing without delays or overregulation that could be harmful to patients. The downstream implications of how VALID and other legislation will impact laboratories, clinicians, and patients warrant close examination.


Subject(s)
Clinical Laboratory Services/legislation & jurisprudence , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Immunocompromised Host , Laboratories, Hospital/legislation & jurisprudence , Pneumonia, Viral/diagnosis , Uncertainty , United States Food and Drug Administration/legislation & jurisprudence , Betacoronavirus/pathogenicity , Congresses as Topic , Health Services Research/legislation & jurisprudence , Humans , Pandemics , Quality Assurance, Health Care , United States
16.
Am J Transplant ; 20(7): 1819-1825, 2020 07.
Article in English | MEDLINE | ID: covidwho-642184

ABSTRACT

There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.


Subject(s)
Coronavirus Infections/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Pneumonia, Viral/complications , Transplant Recipients , Aged , Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Critical Care , Electronic Health Records , Female , Hospitalization , Humans , Immunocompromised Host , Immunosuppression/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/virology , Male , Middle Aged , New York/epidemiology , Pandemics , Pneumonia, Viral/mortality
17.
Curr Opin Infect Dis ; 33(4): 290-297, 2020 08.
Article in English | MEDLINE | ID: covidwho-641651

ABSTRACT

PURPOSE OF REVIEW: Although clinical outcomes in the treatment of aspergillosis have markedly improved with the availability of newer triazoles, the development of resistance to these antifungals, especially in Aspergillus fumigatus, is a growing concern. The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis. RECENT FINDINGS: Resistance may develop through either patient or environmental azole exposure. Environmental exposure is the most prevalent means of resistance development, and these isolates can cause disease in various at-risk groups, which now include those with influenza, and potentially COVID-19. Although current treatment options are limited, newer therapies are in clinical development. These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus. SUMMARY: Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. Certain geographic regions and patient populations appear to be at increased risk for this pathogen. As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. While treatment options are currently limited, new agents under clinical development may offer hope.


Subject(s)
Antifungal Agents/pharmacology , Aspergillosis/immunology , Aspergillus fumigatus/immunology , Coronavirus Infections/immunology , Drug Resistance, Multiple, Fungal/immunology , Pneumonia, Viral/immunology , Triazoles/pharmacology , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/microbiology , Aspergillus fumigatus/drug effects , Betacoronavirus/immunology , Environmental Exposure , Humans , Immunocompromised Host/immunology , Microbial Sensitivity Tests , Pandemics , Triazoles/therapeutic use
19.
Cancer Sci ; 111(9): 3379-3385, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-622503

ABSTRACT

The rapid spread of coronavirus disease 2019 (COVID-19) represented the most serious issue to public health globally. Hematological patients as immunocompromised hosts are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is little information available regarding the clinical features of hematological patients concomitant with COVID-19. In this study, 9 concomitant patients were analyzed for their clinical manifestations, laboratory data, radiological findings, and immunologic features. The median age was 50 years (range, 17-68 years) and 6 patients were male. Seven patients were infected through hospital-associated transmission and other 2 through community-associated transmission. Onset of COVID-19 in all patients occurred during routine treatments for their hematological diseases. Eight patients were classified as moderate and 1 patient as critically ill COVID-19. Four patients died, 1 from leukemia progression, 2 from life-threatening secondary infection, and the other from respiratory failure caused by COVID-19. Abruptly elevated levels of cytokines were often correlated with progressive hematological disease or concurrent bacterial infections. Two patients had atypical computed tomography (CT) imaging findings of COVID-19. The median interval from the first CT scan imaging to improvement in survivors was 40 days (range, 14-51 days). Four of 5 survivors had negative serological tests 1 month after symptom onset. Positive viral load in 4 survivors lasted longer than 45 days. Our results indicated concomitant patients formed a distinct subgroup characterized by atypical clinical features, defective viral clearance, and lower level of SARS-CoV-2-specific Abs. Targeted therapies that impair host humoral immunity should be avoided. These findings will be helpful to tailor appropriate management for the concomitant patients.


Subject(s)
Coronavirus Infections/complications , Hematologic Diseases/complications , Hematologic Diseases/therapy , Immunocompromised Host , Pneumonia, Viral/complications , Adolescent , Adult , Aged , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Young Adult
20.
Br J Haematol ; 190(2): 185-188, 2020 07.
Article in English | MEDLINE | ID: covidwho-626838

ABSTRACT

SARS-CoV-2 infection can cause severe pneumonia (COVID-19). There is evidence that patients with comorbidities are at higher risk of a severe disease course. The role of immunosuppression in the disease course is not clear. In the present report, we first describe two cases of persisting SARS-CoV-2 viraemia with fatal outcome in patients after rituximab therapy.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Rituximab/administration & dosage , Viremia/diagnosis , Aged , B-Lymphocytes/pathology , Betacoronavirus , Coronavirus Infections/complications , Fatal Outcome , Humans , Immunocompromised Host , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Mantle-Cell/complications , Lymphoma, Mantle-Cell/drug therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications
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