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Open accessJournal ArticleDOI: 10.1136/BCR-2020-240765

Possible COVID-19 reinfection in a patient with X-linked agammaglobulinaemia.

04 Mar 2021-Case Reports (BMJ)-Vol. 14, Iss: 3
Abstract: This report highlights the case of a patient with X-linked agammaglobulinaemia (XLA) and resultant bronchiectasis who was discharged from hospital after recovering from real-time reverse transcriptase-PCR positive COVID-19 infection having had a subsequent negative swab and resolution of symptoms, but was readmitted 3 weeks later with recrudescent symptoms and a further positive swab. Although there are reports of COVID-19 infection in XLA, for the first time we report a case of possible reinfection. Lessons learnt from this case include the potential for reinfection of COVID-19 in a patient with a weakened immune system and the importance of repeating COVID-19 swabs in inpatients. Extra caution needs to be taken when providing care in groups of patients who have a weakened or absent immune system.

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5 results found


Open accessJournal ArticleDOI: 10.1080/14760584.2021.1932475
Abstract: INTRODUCTION: : The ongoing SARS-CoV-2 pandemic is a serious threat for the health of immunocompromised patients. Among neutralizing antibody-based therapeutics, convalescent plasma containing polyclonal anti-SARS-CoV-2 immunoglobulins has promising results in both congenital and iatrogenic immunodeficiencies in oncohematological and transplant patients. AREAS COVERED: : This article discusses case reports, case series and controlled studies detailing the efficacy of convalescent plasma in immunocompromised patients. EXPERT OPINION: : Convalescent plasma, when administered at high neutralizing antibody titers, is a safe and effective treatment for frail immunocompromised patients. Genetic monitoring of refractory patients is recommended to intercept intra-host emergence of SARS-CoV-2 variants.

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2 Citations


Open accessJournal ArticleDOI: 10.1038/S41408-021-00546-9
Chiara Cattaneo, Valeria Cancelli, Luisa Imberti1, Kerry Dobbs2  +13 moreInstitutions (2)
Abstract: The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

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Topics: Seroconversion (54%), Rituximab (52%), Follicular lymphoma (52%)

2 Citations


Open accessJournal ArticleDOI: 10.1097/INF.0000000000003360
Abstract: We present a case of a 17-year-old boy with X-linked agammaglobulinemia who had mild disease when initially infected with SARS-CoV-2 but after recovering from acute infection developed fevers and a raised erythrocyte sedimentation rate that persisted for several weeks without any ongoing respiratory symptoms. Multiple nasopharyngeal swabs were found to be negative for SARS-CoV-2 during the febrile period, but typical changes of COVID-19 on high resolution CT chest scan led to the detection of SARS-CoV-2 on RT-PCR in a sample from a bronchoalveolar lavage. His fevers completely resolved after a 5-day course of remdesivir.

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Topics: Bronchoalveolar lavage (50%)

Open accessJournal ArticleDOI: 10.1097/ACI.0000000000000792
Abstract: Purpose of review The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). Recent findings Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. Summary In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit.

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Journal ArticleDOI: 10.1097/MOP.0000000000001062
Abstract: Purpose of review The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused extreme concern for patients with inborn errors of immunity (IEIs). In the first 6 months of the pandemic, the case fatality rate among patients with IEIs resembled that of the general population (9%). This review aims at summarizing what we have learned about the course and outcome of coronavirus disease 2019 (COVID-19) in patients with different IEIs and what this can potentially teach us about the immune mechanisms that could confer protection or predisposition to severe disease. Recent findings A total of 649 patients with IEI and COVID-19 have been reported in the last year and a half, spanning all groups of the International Union of Immunological Societies classification of IEIs. For most patients, the underlying IEI does not represent an independent risk factor for severe COVID-19. In fact, some IEI may even be protective against the severe disease due to impaired inflammation resulting in less immune-mediated collateral tissue damage. Summary We review the characteristics of SARS-CoV-2 infection in a large number of patients with IEI. Overall, we found that combined immunodeficiencies, immune dysregulation disorders, and innate immune defects impairing type I interferon responses are associated with severe disease course.

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Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30154-9
Jasper Fuk-Woo Chan1, Shuofeng Yuan1, Kin-Hang Kok1, Kelvin K. W. To1  +19 moreInstitutions (2)
15 Feb 2020-The Lancet
Abstract: Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).

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Topics: Coronavirus (51%)

5,975 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.2565
Yan Bai, Lingsheng Yao, Tao Wei, Fei Tian1  +3 moreInstitutions (2)
14 Apr 2020-JAMA
Abstract: This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.

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Topics: Asymptomatic carrier (56.99%)

3,104 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMC2001468
Camilla Rothe1, Mirjam Schunk1, Peter Sothmann1, Gisela Bretzel1  +13 moreInstitutions (3)
Abstract: 2019-nCoV Transmission from Asymptomatic Patient In this report, investigators in Germany detected the spread of the novel coronavirus (2019-nCoV) from a person who had recently traveled from China...

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Topics: Asymptomatic Diseases (56.99%), Asymptomatic (52%)

2,923 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2380-Z
Bin Ju1, Qi Zhang2, Jiwan Ge2, Ruoke Wang2  +20 moreInstitutions (4)
26 May 2020-Nature
Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention1-3. The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)2,4-6. Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2.

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Topics: Coronavirus (59%), Viral entry (56.99%), Monoclonal antibody (56%) ... show more

959 Citations


Open accessJournal ArticleDOI: 10.1016/J.IMMUNI.2020.05.002
Nicolas Vabret1, Graham J. Britton1, Conor Gruber1, Samarth Hegde1  +84 moreInstitutions (2)
16 Jun 2020-Immunity
Abstract: \n Abstract\n \n The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.\n \n

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950 Citations


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