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1.
Intern Med J ; 51 Suppl 7: 143-176, 2021 11.
Article in English | MEDLINE | ID: covidwho-1961593

ABSTRACT

Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.


Subject(s)
Aspergillosis , COVID-19 , Adult , Antifungal Agents/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus fumigatus , Child , Drug Resistance, Fungal , Humans , SARS-CoV-2 , Voriconazole/therapeutic use
2.
Nat Commun ; 13(1): 2774, 2022 05 19.
Article in English | MEDLINE | ID: covidwho-1900484

ABSTRACT

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunity , Immunoglobulin G , Immunoglobulin M , Respiratory System , SARS-CoV-2 , Severity of Illness Index , Spike Glycoprotein, Coronavirus
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317943

ABSTRACT

T-cell responses to SARS-CoV-2-derived peptide pools have been documented, however it remains largely unclear whether prominent SARS-CoV-2-specific T cell populations originate from naïve or pre-existing memory sets. As HLA-B*07:02-restricted N105-113 epitope (B7/N105) is the most dominant SARS-CoV-2 CD8+ T-cell specificity to date, we dissected CD8+ T-cell responses directed at this epitope by direct ex vivo analyses in peripheral blood mononuclear cells (PBMCs) from acute and convalescent COVID-19 patients, and pre-pandemic PBMCs, tonsils, lungs and spleens. Using peptide-HLA tetramers, immunodominant B7/N105+CD8+ T-cells were detected at a high frequency (∼2.18x10-4) in COVID-19 patients, comparable to the well-established influenza-specific A2/M158+CD8+ T-cell population. Remarkably, frequencies of B7/N105+CD8+ T-cells were also readily detectable in pre-pandemic PBMCs and tonsils (at 6.55x10-5 and 2.76x10-4, respectively), although they mainly displayed a naïve phenotype, indicating a lack of previous cross-reactive exposures. Ex vivo TCRαβ analyses revealed that a diverse TCRαβ repertoire and promiscuity in αβ TCR pairing underlie such high naïve precursor frequencies of B7/N105+CD8+ T-cells. Overall, our study demonstrates that high precursor frequency and plasticity of TCRα-TCRβ pairing underpin immunodominance of SARS-CoV-2-specific B7/N105+CD8+ T-cell responses and advocates for vaccine strategies which include the nucleocapsid protein to elicit immunodominant CD8+ T-cell responses in HLA-B*07:02 individuals.Funding: This work was supported by theClifford Craig Foundation to KLF and KK, NHMRC Leadership Investigator Grant to KK (1173871), NHMRC Program Grant to DLD (#1132975), Research Grants Council of theHong Kong Special Administrative Region, China (#T11-712/19-N) to KK, the Victorian Government (SJK, AKW), MRFF award (#2002073) to SJK and AKW, MRFFAward (#1202445) to KK, NHMRC program grant 1149990 (SJK) and NHMRC project grant 1162760 (AKW). AKW is supported by Emerging Leadership 1 Investigator Grant (#1173433), JAJ by an NHMRC Early Career Fellowship (ECF) (#1123673), KK by NHMRC SeniorResearch Fellowship (1102792), DLD by a NHMRC Principal Research Fellowship(#1137285) and SJK by NHMRC Senior Principal Research Fellowship (#1136322). CES has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (#792532). JR is supported by an ARC Laureate fellowship. JRH and WZ are supported by the Melbourne Research Scholarship from The University of Melbourne. LH is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne.Ethical Approval: Experiments conformed to the Declaration of Helsinki Principles and theAustralian National Health and Medical Research Council Code of Practice. Written informed consents were obtained from all blood donors prior to the study. Lung and spleen tissues were obtained from deceased organ donors after written informed consents from the next of kin.Written informed consents were obtained from participants’ parental or guardians for underage tonsil tissue donors. The study was approved by the Alfred Hospital (#280/14), Austin Health (HREC/63201/Austin-2020);the University of Melbourne (#2057366.1, #2056901.1,#2056689, #2056761, #1442952, #1955465, and #1443389), the Australian Red CrossLifeblood (ID 2015#8), the Tasmanian Health and Medical (ID H0017479) and the James Cook University (H7886) Human Research Ethics Committees.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313938

ABSTRACT

Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4 + and CD8 + T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.

6.
Open Forum Infect Dis ; 8(9): ofab359, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1405048

ABSTRACT

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR+/CD38+ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2-specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

8.
Intern Med J ; 51(6): 868-872, 2021 06.
Article in English | MEDLINE | ID: covidwho-1280323

ABSTRACT

BACKGROUND: Countries with a high prevalence of COVID-19 have identified a reduction in crude hospital admission rates for non-COVID-19 conditions during the pandemic. There remains a paucity of such data from lower prevalence countries, including Australia. AIMS: To describe the patterns of unplanned hospital daily admission rates during the COVID-19 pandemic in a major Australian metropolitan hospital, with a focus on acute medical presentations including acute coronary syndrome (ACS), stroke and falls. METHODS: This single-centre retrospective analysis analysed hospital admission episodes between 1 March and 30 April 2020 (COVID-19-era) and compared this to a historical cohort during the same period between 2017 and 2019 (pre-COVID-19). Information collected included total admission rates and patient characteristics for ACS, stroke and falls patients. RESULTS: A total of 12 278 unplanned admissions was identified across the study period. The daily admission rate was lower in the COVID-19-era compared with pre-COVID-19 (46.59 vs 51.56 days, P < 0.001). There was also a reduced average daily admission rate for falls (7.79 vs 9.95 days, P < 0.001); however, similar admission rates for ACS (1.52 vs 1.49 days, P = 0.83) and stroke (1.56 vs 1.76 days, P = 0.33). CONCLUSIONS: Public health interventions have been effective in reducing domestic cases of COVID-19 in Australia. At our tertiary metropolitan hospital, we have observed a significant reduction in unplanned hospital admission rates during the COVID-19-era, particularly for falls. Public health messaging needs to focus on educating the public how to seek medical care safely and promptly in the context of the ongoing COVID-19 crisis.


Subject(s)
COVID-19 , Pandemics , Australia/epidemiology , Humans , Retrospective Studies , SARS-CoV-2 , Tertiary Care Centers
9.
Immunity ; 54(5): 1066-1082.e5, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1216346

ABSTRACT

To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαß repertoires and promiscuous αß-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαß diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunodominant Epitopes/immunology , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Adult , Aged , Amino Acid Motifs , CD4-Positive T-Lymphocytes , Child , Convalescence , Coronavirus Nucleocapsid Proteins/chemistry , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immunodominant Epitopes/chemistry , Male , Middle Aged , Phenotype , Phosphoproteins/chemistry , Phosphoproteins/immunology , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/chemistry , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
10.
Front Immunol ; 12: 646095, 2021.
Article in English | MEDLINE | ID: covidwho-1170086

ABSTRACT

Background: The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined. Methods: A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited - blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC). Results: IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06, 35.77) in patients with NIC; and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was amplified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity. Conclusions: Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.


Subject(s)
Bacteremia/blood , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/physiopathology , Interleukin-6/blood , Respiratory Distress Syndrome/blood , Staphylococcal Infections/blood , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Cohort Studies , Comorbidity , Dexamethasone/therapeutic use , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/complications , Severity of Illness Index
11.
Lancet Reg Health West Pac ; 9: 100115, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1117260

ABSTRACT

BACKGROUND: In Australia, COVID-19 diagnosis relies on RT-PCR testing which is relatively costly and time-consuming. To date, few studies have assessed the performance and implementation of rapid antigen-based SARS-CoV-2 testing in a setting with a low prevalence of COVID-19 infections, such as Australia. METHODS: This study recruited participants presenting for COVID-19 testing at three Melbourne metropolitan hospitals during a period of low COVID-19 prevalence. The Abbott PanBioTM COVID-19 Ag point-of-care test was performed alongside RT-PCR. In addition, participants with COVID-19 notified to the Victorian Government were invited to provide additional swabs to aid validation. Implementation challenges were also documented. FINDINGS: The specificity of the Abbott PanBioTM COVID-19 Ag test was 99.96% (95% CI 99.73 - 100%). Sensitivity amongst participants with RT-PCR-confirmed infection was dependent upon the duration of symptoms reported, ranging from 77.3% (duration 1 to 33 days) to 100% in those within seven days of symptom onset. A range of implementation challenges were identified which may inform future COVID-19 testing strategies in a low prevalence setting. INTERPRETATION: Given the high specificity, antigen-based tests may be most useful in rapidly triaging public health and hospital resources while expediting confirmatory RT-PCR testing. Considering the limitations in test sensitivity and the potential for rapid transmission in susceptible populations, particularly in hospital settings, careful consideration is required for implementation of antigen testing in a low prevalence setting. FUNDING: This work was funded by the Victorian Department of Health and Human Services. The funder was not involved in data analysis or manuscript preparation.

13.
Cell Rep Med ; 2(3): 100208, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1065663

ABSTRACT

SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.


Subject(s)
Antibody Formation , COVID-19/immunology , Adaptive Immunity , Adult , Aged , Antibodies, Viral/blood , B-Lymphocytes/cytology , B-Lymphocytes/metabolism , COVID-19/pathology , COVID-19/virology , Female , Humans , Immunity, Innate , Interleukin-18/metabolism , Interleukin-6/metabolism , Male , Middle Aged , Receptors, CXCR3/metabolism , Receptors, Interleukin-6/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Th1 Cells/cytology , Th1 Cells/metabolism , Young Adult
15.
PLoS One ; 15(12): e0243414, 2020.
Article in English | MEDLINE | ID: covidwho-969724

ABSTRACT

OBJECTIVES: We report on the key clinical predictors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and present a clinical decision rule that can risk stratify patients for COVID-19. DESIGN, PARTICIPANTS AND SETTING: A prospective cohort of patients assessed for COVID-19 at a screening clinic in Melbourne, Australia. The primary outcome was a positive COVID-19 test from nasopharyngeal swab. A backwards stepwise logistic regression was used to derive a model of clinical variables predictive of a positive COVID-19 test. Internal validation of the final model was performed using bootstrapped samples and the model scoring derived from the coefficients, with modelling performed for increasing prevalence. RESULTS: Of 4226 patients with suspected COVID-19 who were assessed, 2976 patients underwent SARS-CoV-2 testing (n = 108 SARS-CoV-2 positive) and were used to determine factors associated with a positive COVID-19 test. The 7 features associated with a positive COVID-19 test on multivariable analysis were: COVID-19 patient exposure or international travel, Myalgia/malaise, Anosmia or ageusia, Temperature, Coryza/sore throat, Hypoxia-oxygen saturation < 97%, 65 years or older-summarized in the mnemonic COVID-MATCH65. Internal validation showed an AUC of 0.836. A cut-off of ≥ 1.5 points was associated with a 92.6% sensitivity and 99.5% negative predictive value (NPV) for COVID-19. CONCLUSIONS: From the largest prospective outpatient cohort of suspected COVID-19 we define the clinical factors predictive of a positive SARS-CoV-2 test. The subsequent clinical decision rule, COVID-MATCH65, has a high sensitivity and NPV for SARS-CoV-2 and can be employed in the pandemic, adjusted for disease prevalence, to aid COVID-19 risk-assessment and vital testing resource allocation.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Clinical Decision-Making , Models, Biological , SARS-CoV-2 , Adult , Aged , Australia/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Female , Humans , Male , Middle Aged , Prospective Studies
16.
Transplant Proc ; 52(9): 2676-2683, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-745913

ABSTRACT

Liver transplant recipients may be at increased risk for adverse outcomes with coronavirus disease 2019 (COVID-19) infection because of chronic immunosuppression and associated comorbidities. There is a paucity of literature describing clinical presentation, treatments, and outcomes in liver transplant recipients with COVID-19. A systematic search was performed for articles published up to June 15, 2020, revealing 223 liver transplant recipients with COVID-19 in 15 studies. Patients most commonly presented with fever (66.7%), dyspnea (34.0%), and diarrhea (28.4%). Of these, 77.7% required hospitalization, 24% had mild disease, 40% had moderate disease, and 36% had severe disease. Immunosuppression was modified in 32.8% of recipients. The case fatality rate was 19.3%. Dyspnea on presentation, diabetes mellitus, and age 60 years or older were significantly associated with increased mortality (P ≤ .01) with a trend to higher mortality rate observed in those with hypertension and those receiving corticosteroids at the time of COVID-19 diagnosis. The median time from symptoms to death was 11.5 days (2-45 days). In conclusion, liver transplant recipients with severe acute respiratory syndrome coronavirus 2 are overrepresented with regard to severe disease and hospitalizations. Older liver transplant patients with diabetes mellitus or hypertension, who are on maintenance corticosteroids, with a diagnosis of COVID-19 and describing breathlessness should be aggressively monitored for signs of deterioration because of the risk for mortality.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/mortality , Immunocompromised Host , Liver Transplantation/mortality , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Aged , Betacoronavirus , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , Risk Factors , SARS-CoV-2 , Transplant Recipients
17.
J Allergy Clin Immunol ; 146(3): 518-534.e1, 2020 09.
Article in English | MEDLINE | ID: covidwho-737831

ABSTRACT

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4+ and CD8+ T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/therapy , Cytokine Release Syndrome/virology , Immunomodulation , Interleukin-6/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Betacoronavirus , COVID-19 , Cytokine Release Syndrome/immunology , Humans , Pandemics , SARS-CoV-2 , Sepsis/immunology
18.
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