SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity

Wei, Jia; Zhao, Jianping; Han, Meifang; Fang, Meng; Zhou, Jianfeng

doi:10.1136/jitc-2020-000862

Cited by 57 publications

(40 citation statements)

References 25 publications

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“…Immunocompromised patients infected with SARS-CoV-2, especially those with comorbidities, may have a higher risk for severe outcomes than the general population [6][7][8]. Individuals with autoimmune diseases have an increased risk for infections [9,10].…”

Section: Key Pointsmentioning

confidence: 99%

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

et al. 2021

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Background Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). Objective The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. Methods The IBM ® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. Results 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. Conclusions Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

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Section: Key Pointsmentioning

confidence: 99%

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

et al. 2021

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“…If the PCR test result is positive, surgery should be postponed until at least 2 weeks after COVID-19 symptom. Wei et al [ 17 ] reported two immunocompromised patients with severe COVID-19 pneumonia. One patient generated specific anti-immunoglobulin G antibodies of SARS-CoV-2 after 2 weeks of treatment, and could discharge from the hospital on day 42.…”

Section: Introductionmentioning

confidence: 99%

“…One patient generated specific anti-immunoglobulin G antibodies of SARS-CoV-2 after 2 weeks of treatment, and could discharge from the hospital on day 42. However, the other failed to obtain specific antibodies of SARS-CoV-2, and eventually died due to respiratory failure [ 17 ]. In immunocompromised patients, the surgery may need to be postponed for longer (at least 24 days), because the time to clear SARS-CoV-2 tends to be longer [ 14 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Preoperative assessment for scheduling surgery during the coronavirus disease pandemic

Suehiro

2021

J Anesth

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On Mar 11, 2020, the World Health Organization declared coronavirus disease , caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a pandemic. Because COVID-19 has a pre-symptomatic period of up to 2 weeks, SARS-CoV-2 infection has continued to spread. Some individuals with SARS-CoV-2 infection have a severe clinical course, while most individuals have mild or moderate symptoms. Because SARS-CoV-2 is transmitted via droplets and secretions, anesthesiologists have higher risks of infection, especially during airway management. Therefore, general anesthesia requiring airway management can be a challenging procedure for anesthesiologists. During the pandemic, many elective surgeries have been postponed or cancelled in most affected countries. Recently, the number of elective surgeries is gradually recovering from the effect of the COVID-19 pandemic, and hence, safe clinical practice and protocols to prevent SARS-CoV-2 transmission to medical staff should be established. This mini-review focuses on the preoperative assessment and decision with regard to scheduling surgery in elective and emergency cases during the COVID-19 pandemic. A standardized questionnaire and algorithm regarding COVID-19 should be used to assess surgical patients preoperatively as it increases the reproducibility and accuracy of the decision whether to proceed with surgery.

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“…impairment, such as that resulting from cancer, has been associated with prolonged SARS-CoV-2 shedding and the seeding of "super-spreader" events [14][15][16][17][18]. As we consider host-directed small molecules as candidates for antiviral therapies, it remains critically important to assess their impact on both dependency factors and restriction factors before they are deployed to slow virus transmission and/or prevent viral pathogenesis in humans.…”

mentioning

confidence: 99%

Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2

Shi

Chiramel

Majdoul

et al. 2021

Preprint

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Infection by SARS-CoV-2 generally causes mild symptoms but can lead to severe disease and death in certain populations, including the immunocompromised. Drug repurposing efforts are underway to identify compounds that interfere with SARS-CoV-2 replication or the immunopathology it can elicit. Rapamycin is among those being currently tested in clinical trials for impacts on COVID-19 severity. While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple clinical settings, including cancer, we previously found that rapamycin can increase the susceptibility of cells to infection by Influenza A virus. In this study, we tested the impact of rapalogs on cellular susceptibility to SARS-CoV-2 infection. We report that rapamycin and rapalogs increased SARS-CoV-2 titers in human cervical epithelial and lung epithelial cell lines to different extents, and a similar pattern of enhancement was observed using pseudovirus incorporating viral fusion proteins from SARS-CoV-2, SARS-CoV, MERS, and Influenza A Virus. Rapalogs also promoted cell entry driven by SARS-CoV-2 Spike in nasal cells and primary small airway cells, representing proximal and distal ends of the human respiratory tract, respectively. Interestingly, cell entry enhancement by the rapalog ridaforolimus was cell type-dependent, revealing a previously unrecognized functional divergence between rapalogs. The differential activity of rapalogs was associated with their capacity to induce the degradation of interferon-inducible transmembrane (IFITM) proteins, restriction factors that broadly inhibit virus infection. Our findings will spur the development of mTOR inhibitors that do not suppress the first line of antiviral defense in cells.

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SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity

Cited by 57 publications

References 25 publications

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

Preoperative assessment for scheduling surgery during the coronavirus disease pandemic

Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2

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