The importance of chest CT severity score and lung CT patterns in risk assessment in COVID-19-associated pneumonia: a comparative study.

Introduction: Chest computed tomography (CT) is suitable to assess morphological changes in the lungs. Chest CT scoring systems (CCTS) have been developed and use in order to quantify the severity of pulmonary involvement in COVID-19. CCTS has also been correlated with clinical outcomes. Here we wished to use a validated, relatively simple CTSS to assess chest CT patterns and to correlate CTSS with clinical outcomes in COVID-19. Patients and methods: Altogether 227 COVID-19 cases underwent chest CT scanning using a 128 multi-detector CT scanner (SOMATOM Go Top, Siemens Healthineers, Germany). Specific pathological features, such as ground-glass opacity (GGO), crazy-paving pattern, consolidation, fibrosis, subpleural lines, pleural effusion, lymphadenopathy and pulmonary embolism were evaluated. CTSS developed by Pan et al. (CTSS-Pan) was applied. CTSS and specific pathologies were correlated with demographic, clinical and laboratory data, A-DROP scores, as well as outcome measures. We compared CTSS-Pan to two other CT scoring systems. Results: The mean CTSS-Pan in the 227 COVID-19 patients was 14.6 ± 6.7. The need for ICU admission (p < 0.001) and death (p < 0.001) were significantly associated with higher CTSS. With respect to chest CT patterns, crazy-paving pattern was significantly associated with ICU admission. Subpleural lines exerted significant inverse associations with ICU admission and ventilation. Lymphadenopathy was associated with all three outcome parameters. Pulmonary embolism led to ICU admission. In the ROC analysis, CTSS>18.5 significantly predicted admission to ICU (p = 0.026) and CTSS>19.5 was the cutoff for increased mortality (p < 0.001). CTSS-Pan and the two other CTSS systems exerted similar performance. With respect to clinical outcomes, CTSS-Pan might have the best performance. Conclusion: CTSS may be suitable to assess severity and prognosis of COVID-19-associated pneumonia. CTSS and specific chest CT patterns may predict the need for ventilation, as well as mortality in COVID-19. This can help the physician to guide treatment strategies in COVID-19, as well as other pulmonary infections.

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.

A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans.We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors. The HSRs in 15 subjects were graded and correlated with anti-PEG IgG/IgM, just as the anti-S and anti-PEG Ab levels with each other. The impacts of gender, allergy, mastocytosis and use of cosmetics were also analyzed. Serial testing of two or more plasma samples showed substantial individual variation of anti-S Ab levels after repeated vaccinations, just as the levels of anti-PEG IgG and IgM, which were over baseline in 98-99 % of unvaccinated individuals. About 3-4 % of subjects in the strongly left-skewed distribution had 15-45-fold higher values than the median, referred to as anti-PEG Ab supercarriers. Both vaccines caused significant rises of anti-PEG IgG/IgM with >10-fold rises in about âˆ¼10 % of Comirnaty, and all Spikevax recipients. The anti-PEG IgG and/or IgM levels in the 15 vaccine reactors (3 anaphylaxis) were significantly higher compared to nonreactors. Serial testing of plasma showed significant correlation between the booster injection-induced rises of anti-S and anti-PEG IgGs, suggesting coupled anti-S and anti-PEG immunogenicity.Conclusions: The small percentage of people who have extremelevels of anti-PEG Ab in their blood may be at increased risk for HSRs/anaphylaxis to PEGylated vaccines and other PEGylated injectables. This risk might be further increased by the anti-PEG immunogenicity of these vaccines. Screening for anti-PEG Ab "supercarriers" may help predicting reactors and thus preventing these adverse phenomena.

The Alterations of Serum N-glycome in Response to SARS-CoV-2 Vaccination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global concern since its outbreak in 2019, with one of the main solutions being vaccination. Altered glycosylation has been described in patients after SARS-CoV-2 infection, while the effect of vaccination on serum glycoproteins remained unexplored. In this study, total serum glycosylation was analyzed in patients after SARS-CoV-2 infection and/or mRNA vaccination in order to identify potential glycosylation-based alterations. Enzyme-linked immunosorbent assay was applied to identify post-COVID-19 and post-Vaccinated patients and rule out potential outliers. Serum samples were deglycosylated by PNGase F digestion, and the released glycans were fluorescently derivatized using procainamide labeling. Solid-phase extraction was used to purify the labeled glycans followed by the analysis of hydrophilic-interaction liquid chromatography with fluorescence and mass-spectrometric detection. Alterations of serum N-glycome in response to SARS-CoV-2 infection and mRNA vaccination were revealed by linear discriminant analysis.

Tocilizumab in Combination with Corticosteroids in COVID-19 Pneumonia: A Single-Centre Retrospective Controlled Study.

Introduction: Interleukin 6 receptor inhibition by tocilizumab (TCZ) has been effectively used worldwide for the treatment of multisystem inflammatory syndrome (MIS) associated with COVID-19. In this single centre study, we compared the outcome of COVID-19 pneumonia in TCZ-treated vs. untreated (control) patients. We wished to compare TCZ administration in the general ward vs. in the intensive care unit (ICU). We also studied the role of a consulting rheumatologist in the management of severe COVID-19 pneumonia. Patients and methods: In our patients, COVID-19 pneumonia was confirmed by SARS-CoV-2 PCR, chest X-ray, and CT. We compared patients selected for TCZ treatment with TCZ-untreated age- and sex-matched controls. All patients received corticosteroids. In the TCZ-treated group, patients received one or two doses of TCZ 8 mg/kg IV in combination with corticosteroids. We recorded age, sex, symptom duration, oxygen saturation (SaO2), partial arterial oxygen pressure (PaO2), total white blood cell (WBC), absolute neutrophil, absolute lymphocyte and platelet counts, CRP, ferritin, IL-6, LDH, procalcitonin (PCT), and D-dimer. The primary outcome parameters were the need for ICU, ventilation, death, and time of hospitalisation. Results: Altogether, 104 patients, 52 TCZ-treated and 52 TCZ-untreated, were included in this study. At baseline, the TCZ-treated patient group indeed had more pronounced COVID-19-related MIS compared to controls. Consultation with a rheumatologist was performed in 60% vs. 40% of cases. Nineteen patients (37%) received one, while 33 (63%) received two TCZ doses. TCZ was administered to 28 patients (54%) in the general ward and to 24 (46%) in the ICU. TCZ treatment was found to be safe in our COVID-19 pneumonia patients. TCZ treatment favourably influenced MIS biomarkers, and was associated with better clinical outcomes compared to controls. Patients receiving TCZ treatment in combination with corticosteroids already in the general ward exerted much better outcomes than those treated in the ICU. Consultation with a rheumatologist also improved outcome. Conclusions: We successfully used TCZ in combination with corticosteroids in Hungarian COVID-19 pneumonia patients. We pointed out the importance of early treatment already in the general ward, and the involvement of a rheumatologist in making treatment decisions.

Severity and prognostic factors of SARS-CoV-2-induced pneumonia: The value of clinical and laboratory biomarkers and the A-DROP score.

Introduction: Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavorable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods: Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results: At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer, and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN, and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p < 0.05). Conclusion: Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.

Severity and prognostic factors of SARS-CoV-2-induced pneumonia: The value of clinical and laboratory biomarkers and the A-DROP score

Introduction Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavorable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer, and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN, and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p < 0.05). Conclusion Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.

A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor.

A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans.

[Treatment options for enormous carotid thrombus as a complication of SARS-CoV-2 infection]. / SARS-Cov-2-fertozés szövodményeként kialakult enormis nagyságú carotisthrombus kezelési lehetoségei.

In SARS-CoV-2 positive patients with corresponding neurological symptoms the presence of carotid bifurcation macrothrombus should always be considered. Hypercoagulopathy caused by viral endotheliitis, systemic inflammation and cytokine storm play an important role in its development. Here we present two patients treated with different treatment strategies because of carotid bifurcation macrothrombus as a complication of SARS-CoV-2 infection. In both cases, the soft macrothrombus was eliminated and the patients' neurological condition were improved. Intravenous thrombolysis, acute carotid stenting with embolic filter protection device and mechanical thrombectomy with aspiration are effective treatments.