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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), antireceptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of [greater than or equal to] 160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was [greater than or equal to] 80% when anti-RBD or anti-ECD titers were [greater than or equal to] 1:1350. Of all donors, 37% lacked VN titers of [greater than or equal to] 160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of [greater than or equal to] 1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of [greater than or equal to] 1:160, and all of them had anti-RBD titers of [greater than or equal to] 1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of [greater than or equal to] 1:1350 may provide critical information about protection against COVID-19 disease., Introduction The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) disease, has spread globally and is now responsible for massive [...]

BACKGROUND. Understanding outcomes and immunologic characteristics of cellular therapy recipients with SARS-CoV-2 is critical to performing these potentially life-saving therapies in the COVID-19 era. In this study of recipients of allogeneic (Allo) and autologous (Auto) hematopoietic cell transplant and CD19-directed chimeric antigen receptor T cell (CAR T) therapy at Memorial Sloan Kettering Cancer Center, we aimed to identify clinical variables associated with COVID-19 severity and assess lymphocyte populations. METHODS. We retrospectively investigated patients diagnosed between March 15, 2020, and May 7, 2020. In a subset of patients, lymphocyte immunophenotyping, quantitative real-time PCR from nasopharyngeal swabs, and SARS-CoV-2 antibody status were available. RESULTS. We identified 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days; IQR, 354-1611 days). Overall survival at 30 days was 78%. Clinical variables significantly associated with the composite endpoint of nonrebreather or higher oxygen requirement and death (n events = 25 of 77) included number of comorbidities (HR 5.41, P = 0.004), infiltrates (HR 3.08, P = 0.032), and neutropenia (HR 1.15, P = 0.04). Worsening graft-versus-host disease was not identified among Allo recipients. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Antibody responses were seen in a subset of patients. CONCLUSION. In this series of Allo, Auto, and CAR T recipients, we report overall favorable clinical outcomes for patients with COVID-19 without active malignancy and provide preliminary insights into the lymphocyte populations that are key for the antiviral response and immune reconstitution. FUNDING. NIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748., Introduction As of June 2, 2020, there were over 1.8 million confirmed cases of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in [...]

BACKGROUND. Marked progress is achieved in understanding the physiopathology of coronavirus disease 2019 (COVID-19), which caused a global pandemic. However, the [CD4.sup.+] T cell population critical for antibody response in COVID-19 is poorly understood. METHODS. In this study, we provided a comprehensive analysis of peripheral [CD4.sup.+] T cells from 13 COVID-19 convalescent patients, defined as confirmed free of SARS-CoV-2 for 2 to 4 weeks, using flow cytometry and magnetic chemiluminescence enzyme antibody immunoassay. The data were correlated with clinical characteristics. RESULTS. We observed that, relative to healthy individuals, convalescent patients displayed an altered peripheral [CD4.sup.+] T cell spectrum. Specifically, consistent with other viral infections, cTfh1 cells associated with SARS-CoV-2-targeting antibodies were found in COVID-19 covalescent patients. Individuals with severe disease showed higher frequencies of Tem and Tfh-em cells but lower frequencies of Tcm, Tfh-cm, Tfr, and Tnaive cells, compared with healthy individuals and patients with mild and moderate disease. Interestingly, a higher frequency of cTfh-em cells correlated with a lower blood oxygen level, recorded at the time of admission, in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of [CD4.sup.+] T cells in the long-term and explain the highest ratio of class-switched virus-specific antibody producing individuals found in our severe COVID-19 cohort. CONCLUSION. Our study demonstrated a close connection between [CD4.sup.+] T cells and antibody production in COVID-19 convalescent patients. FUNDING. Six Talent Peaks Project in Jiangsu Province and the National Natural Science Foundation of China (NSFC)., Introduction Newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 13 million people and caused more than 500,000 deaths globally (1-3). In the hospital, test-positive individuals with [...]

Although corticosteroids dampen the dysregulated immune system and sometimes are prescribed as an adjunctive treatment for pneumonia, their effectiveness in the treatment of coronavirus disease 2019 (COVID-19) remains controversial. In this issue of the JCI, Liu and Zhang et al. evaluated corticosteroid treatment in more than 400 patients with severe COVID-19. The authors assessed subjects retrospectively for cardiac and liver injury, shock, ventilation, mortality, and viral clearance. Corticosteroids in severe COVID-19-related acute respiratory distress syndrome (ARDS) were associated with increased mortality and delayed viral clearance. Here, we consider how to reconcile the negative effects of corticosteroids revealed by Liu and Zhang et al. with the favorable effects (reduced mortality) that were described in the RECOVERY trial. We posit that treatment timing, dosage, and COVID-19 severity determine immune response and viral outcome. Patients with moderate-to-severe COVID-19 pneumonia are likely to benefit from moderate-dose corticosteroid treatment when administered relatively late in the disease course., Corticosteroids in the treatment of viral pneumonia The effects of corticosteroids in the treatment of viral pneumonia and the acute respiratory distress syndrome (ARDS) have been the subject of controversy [...]

COVID-19 spans a wide range of symptoms, sometimes with profound immune system involvement. How immune cell subsets change during the disease course and with disease severity needs further study. While myeloid cells have been shown to initiate and maintain responses to pneumonia and lung inflammation, often playing a role in resolution, their involvement with COVID-19 remains unknown. In this issue of the JCI, Sanchez-Cerrillo and Landete et al. investigated DCs and monocytes from blood and bronchial secretions of patients with varying COVID-19 severity and with healthy controls. The authors conclude that circulating monocytes and DCs migrate from the blood into the inflamed lungs. While sampling differences in sex, collection timing, bacteria/fungal infection, and corticosteroid treatment limit interpretation, we believe that reprogramming monocyte or macrophages by targeting immunometabolism, epigenetics, or the cytokine milieu holds promise in resolving lung inflammation associated with COVID-19., Introduction COVID-19 disease morbidity and mortality have swept the globe since early 2020. The role of the immune response in SARS-CoV-2 pathogenesis and its determinants for the clinical course and [...]

Coronavirus disease 2019 (COVID-19) has devastated the global community since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in late 2019. Most COVID-19 cases occur in adults, and a [...]

* Context.--The coronavirus disease 19 (COVID-19) pandemic is placing unparalleled burdens on regional and institutional resources in medical facilities across the globe. This disruption is causing unprecedented downstream effects to traditionally established channels of patient care delivery, including those of essential anatomic pathology services. With Washington state being the initial North American COVID-19 epicenter, the University of Washington in Seattle has been at the forefront of conceptualizing and implementing innovative solutions in order to provide uninterrupted quality patient care amidst this growing crisis. Objective.--To conduct a rapid validation study assessing our ability to reliably provide diagnostic neuropathology services via a whole slide imaging (WSI) platform as part of our departmental COVID-19 planning response. Design.--This retrospective study assessed diagnostic concordance of neuropathologic diagnoses rendered via WSI as compared to those originally established via traditional histopathology in a cohort of 30 cases encompassing a broad range of neurosurgical and neuromuscular entities. This study included the digitalization of 93 slide preparations, which were independently examined by groups of board-certified neuropathologists and neuropathology fellows. Results.--There were no major or minor diagnostic discrepancies identified in either the attending neuropathologist or neuropathology trainee groups for either the neurosurgical or neuromuscular case cohorts. Conclusions.--Our study demonstrates that accuracy of neuropathologic diagnoses and interpretation of ancillary preparations via WSI are not inferior to those generated via traditional microscopy. This study provides a framework for rapid subspecialty validation and deployment of WSI for diagnostic purposes during a pandemic event. doi: 10.5858/arpa.2020-0372-SA, On December 29, 2019, official reports describing a cluster of patients suffering from a severe novel pneumonia of unknown etiology initially surfaced from Wuhan (Hubei province) in the People's Republic [...]

The first coronavirus disease (COVID-19) case in South Korea was confirmed on January 20, 2020 (1). In the city of Daegu, the disease spread rapidly within a church community after [...]

Evaluation of the effectiveness of mask-wearing to protect healthy persons in the general public from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease [...]

P131 Resilience and frailty in people living with HIV during the lockdown experience in Italy in March-May 2020: are they two complementary constructs? G Guaraldi (1); J Milic (2); G [...]

Mass global events, such as our current public health crisis in the face of the COVID-19 pandemic and the economic shocks that have followed, are disruptive in nature. As in [...]

The disease spectrum of coronavirus disease 2019 (COVID-19) ranges from no symptoms to multisystem failure and death. Characterization of virus-specific immune responses to severe acute respiratory coronavirus 2 (SARS-CoV-2) is key to understanding disease pathogenesis, but few studies have evaluated T cell immunity. In this issue of the JCI, Sattler and Angermair et al. sampled blood from subjects with COVID-19 and analyzed the activation and function of virus antigen-specific [CD4.sup.+] T cells. T cells that failed to respond to peptides from the membrane, spike, or nucleocapsid proteins were more common in subjects who died. In those whose T cells had the capacity to respond, older patients with comorbidity had larger numbers of activated T cells compared with patients who had fewer risk factors, but these cells showed impaired IFN-[gamma] production. This cross-sectional study relates activated T cell responses to patient risk factors and outcome. However, T cell response trajectory over the disease course remains an open question., Introduction The adaptive immune response is critical for virus clearance and eventual recovery from virus infection, but regulation of this response is required because inflammation can also contribute to immune-mediated [...]

Individuals with coronavirus disease 2019 (COVID-19) can develop pneumonia and a severe inflammatory response with excessive cytokine release known as the cytokine storm. The JAK inhibitor baricitinib, used to treat rheumatoid arthritis, reduces inflammation by modifying the cytokine pathway. In this issue of theJ CI, Bronte, Ugel, and colleagues performed an observational longitudinal study to evaluate the use of baricitinib in 20 patients with COVID-19. The treated patients showed reduced levels of plasma IL-6, TNF, IL-1[beta], and phosphorylated STAT3 as well as swift lymphocyte restoration. Notably, these patients had a dramatically favorable clinical outcome. While bias can plague uncontrolled research, this study has biological credibility and warrants randomized, controlled studies., Observational studies In 2020, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) took the world by storm and demanded immediate solutions from the biomedical research community. The first responses were a series [...]

Even though the first wave of COVID-19 cases is still happening, health experts warn that once the weather gets cooler in the fall, a second wave of cases is likely [...]

COVID-19 altered the way the American public lived their lives,- the way they worked, ate, socialized, traveled, and ultimately received their health care. Family Medicine largely closed its doors to [...]

Environmental health professionals are the second largest part of the local public health workforce behind nursing. To support this essential workforce during these uncertain times, NEHA conducted a rapid needs [...]

LETTER FROM LUNDU Otto Steinmayer P.O. Box 13 94500 Lundu, Sarawak Malaysia This time around my Letter must be brief and sketchy, for two reasons. First, I was out of [...]

Byline: Vivek. Tandon, Amol. Raheja Coronavirus disease (COVID-19) has posed immense challenges for healthcare workers, among them are procedures related to suctioning of bodily fluids during surgery or intensive care. [...]

To the Editor.--More than 6 million confirmed cases of coronavirus disease 2019 (COVID-19) have been identified worldwide, and a number of case reports (1-5) have indicated that COVID-19 has the [...]

The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care delivery and has resulted in a backlog of patients needing surgery. There is a lack of experience and guidance in dealing with this increased demand on an already overburdened health care system. We created an online tool (www.covidbacklog.com) that helps surgeons explore how resource allocation within their group will affect wait times for patients. After inputting a handful of readily available variables, the computer program generates a forecast of how long it will take to see the backlog of patients. This information could be used to allow surgical groups to run simulations to explore different resource allocation strategies in order to help prevent downstream consequences of delayed patient care., The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on health care delivery. A recently published global study surveyed neurosurgeons from 60 countries, and more than half of [...]

O421 HIV, ART and COVID-19: interplay and interactions C Sabin (1); L Waters (2); A Sparrowhawk (3); A Owen (4) and M Cevik (5) (1) University College London, London, UK. [...]

The impact of the COVID-19 pandemic on millions of people and the U.S. economy has created unprecedented demand on health and human services (H/HS) agencies. At the same time, COVID-19 [...]