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2.
BMC Infect Dis ; 20(1): 500, 2020 Jul 11.
Article in English | MEDLINE | ID: covidwho-640102

ABSTRACT

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Adult , Antibody Formation , Antiviral Agents/therapeutic use , B-Lymphocytes/immunology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Hospitals , Humans , Immunity, Humoral , Indoles/therapeutic use , Male , Nucleotidyltransferases/genetics , Pandemics , Patient Discharge , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Recurrence , SARS-CoV-2 , Ventilators, Mechanical
3.
J Allergy Clin Immunol ; 146(1): 137-146.e3, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-637807

ABSTRACT

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.


Subject(s)
Coronavirus Infections/drug therapy , Janus Kinase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Pyrazoles/therapeutic use , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Nitriles , Pandemics , Pneumonia, Viral/mortality , Pyrimidines , SARS-CoV-2 , Single-Blind Method , Treatment Outcome , COVID-19 Drug Treatment
4.
Cell Mol Immunol ; 17(9): 992-994, 2020 09.
Article in English | MEDLINE | ID: covidwho-630398
5.
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 , COVID-19 , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Young Adult
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