The neutralizing response to SARS-CoV-2 Omicron variants BA.1 and BA.2 in COVID-19 patients and homologous and heterologous vaccinees.

The rapid replacement of Omicron BA.1 by BA.2 sublineage is very alarming, raising the question of whether BA.2 can escape the immunity acquired after BA.1 infection. We compared the neutralizing activity toward the Omicron BA.1 and BA.2 sub-lineages in five groups: COVID-19 patients; subjects who had received two doses of mRNA vaccine; subjects naturally infected with SARS-CoV-2 who had received two doses of mRNA; and subjects who had received three doses of homologous or heterologous vaccine. The results obtained highlight the importance of vaccine boosters in eliciting neutralizing antibody responses against Omicron sub-lineages, and suggest that the adenovirus vectored vaccine elicits a lower response against BA.1 than against BA.2 sub-lineage.

Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination.

Background: The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods: Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results: In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions: Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations.

The SARS-CoV-2 Omicron variant has rapidly replaced the Delta variant of concern. This new variant harbors worrisome mutations on the spike protein, which are able to escape the immunity elicited by vaccination and/or natural infection. To evaluate the impact and susceptibility of different serum samples to the Omicron variant BA.1, samples from COVID-19 patients and vaccinated individuals were tested for their ability to bind and neutralize the original SARS-CoV-2 virus and the Omicron variant BA.1. COVID-19 patients show the most drastic reduction in Omicron-specific antibody response in comparison with the response to the wild-type virus. Antibodies elicited by a triple homologous/heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1. Overall, these findings confirm that vaccination of COVID-19 survivors and booster dose to vaccinees with mRNA vaccines is the correct strategy to enhance the antibody cross-protection against Omicron variant BA.1.

Robotic-assisted resection of pelvic mesorectum lipoma during the COVID-19 pandemic: a case report.

Mesorectal lipoma is a rare, usually asymptomatic tumor. The best treatment is R0 resection but the previous literature reports different approaches. Robotic surgery allows for an accurate intervention, with a faster postoperative course, less risk of infection and need for transfusions, a faster return to normal daily activities and the best esthetic result. We describe a case of a 43-year-old female with a large lipoma with dislocation of the vagina, rectum and distal sigmoid colon, potentially malignant, successfully treated by robotic excision, which was safe, effective and well tolerated by the patient.

Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients.

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

Characterization of antibody response in asymptomatic and symptomatic SARS-CoV-2 infection.

SARS-CoV-2 pandemic is causing high morbidity and mortality burden worldwide with unprecedented strain on health care systems. To investigate the time course of the antibody response in relation to the outcome we performed a study in hospitalized COVID-19 patients. As comparison we also investigated the time course of the antibody response in SARS-CoV-2 asymptomatic subjects. Study results show that patients produce a strong antibody response to SARS-CoV-2 with high correlation between different viral antigens (spike protein and nucleoprotein) and among antibody classes (IgA, IgG, and IgM and neutralizing antibodies). The antibody peak is reached by 3 weeks from hospital admission followed by a sharp decrease. No difference was observed in any parameter of the antibody classes, including neutralizing antibodies, between subjects who recovered or with fatal outcome. Only few asymptomatic subjects developed antibodies at detectable levels.

Reopening the country: Recommendations for nuclear medicine departments.

The best practices for nuclear medicine departments to operate safely during the COVID-19 pandemic have been debated in the literature recently. However, as many governments have started to ease restrictions in activity due to COVID-19, a set of guidelines is needed to resume routine patient care throughout the world. The nonessential or elective procedures which were previously postponed or canceled during the COVID-19 pandemic will gradually restart in the following weeks despite the continued risks. In this paper, we aim to review some of the most effective general precautions to restart the regular nuclear medicine operations safely.

Prognostic value of CT integrated with clinical and laboratory data during the first peak of the COVID-19 pandemic in Northern Italy: A nomogram to predict unfavorable outcome.

PURPOSE: To evaluate the prognostic role of chest computed tomography (CT), alone or in combination with clinical and laboratory parameters, in COVID-19 patients during the first peak of the pandemic. METHODS: A retrospective single-center study of 301 COVID-19 patients referred to our Emergency Department (ED) from February 25 to March 29, 2020. At presentation, patients underwent chest CT and clinical and laboratory examinations. Outcomes included discharge from the ED after improvement/recovery (positive outcome), or admission to the intensive care unit or death (poor prognosis). A visual quantitative analysis was formed using two scores: the Pulmonary Involvement (PI) score based on the extension of lung involvement, and the Pulmonary Consolidation (PC) score based on lung consolidation. The prognostic value of CT alone or integrated with other parameters was studied by logistic regression and ROC analysis. RESULTS: The impact of the CT PI score [≥15 vs. ≤ 6] on predicting poor prognosis (OR 5.71 95 % CI 1.93-16.92, P = 0.002) was demonstrated; no significant association was found for the PC score. Chest CT had a prognostic role considering the PI score alone (AUC 0.722) and when evaluated with demographic characteristics, comorbidities, and laboratory data (AUC 0.841). We, therefore, developed a nomogram as an easy tool for immediate clinical application. CONCLUSIONS: Visual analysis of CT gives useful information to physicians for prognostic evaluations, even in conditions of COVID-19 emergency. The predictive value is increased by evaluating CT in combination with clinical and laboratory data.

Increased incidence of interstitial pneumonia detected on [18F]-FDG-PET/CT in asymptomatic cancer patients during COVID-19 pandemic in Lombardy: a casualty or COVID-19 infection?

PURPOSE: The study aimed to compare the incidence of interstitial pneumonia on [18F]-FDG PET/CT scans between two 6-month periods: (a) the COVID-19 pandemic peak and (b) control period. Secondly, we compared the incidence of interstitial pneumonia on [18F]-FDG PET/CT and epidemiological data from the regional registry of COVID-19 cases. Additionally, imaging findings and the intensity of [18F]-FDG PET/CT uptake in terms of maximum standardized uptake value (SUVmax) were compared. METHODS: We retrospectively analyzed [18F]-FDG PET/CT scans performed in cancer patients referred to nuclear medicine of Humanitas Gavazzeni in Bergamo from December 2019 to May 2020 and from December 2018 to May 2019. The per month incidence of interstitial pneumonia at imaging and the epidemiological data were assessed. To evaluate the differences between the two symmetric groups (period of COVID-19 pandemic and control), the stratified Cochran-Mantel-Haenszel test was used. Chi-square test or Fisher's exact test and t test or Wilcoxon test were performed to compare the distributions of categorical and continuous variables, respectively. RESULTS: Overall, 1298 patients were included in the study. The two cohorts-COVID-19 pandemic (n = 575) and control (n = 723)-did not statistically differ in terms of age, disease, or scan indication (p > 0.05). Signs of interstitial pneumonia were observed in 24 (4.2%) and 14 patients (1.9%) in the COVID-19 period and the control period, respectively, with a statistically significant difference (p = 0.013). The level of statistical significance improved further when the period from January to May was considered, with a peak in March (7/83 patients, 8.4% vs 3/134 patients, 2.2%, p = 0.001). The curve of interstitial pneumonia diagnosis overlapped with the COVID-19 incidence in the area of Lombardy (Spearman correlation index was equal to 1). Imaging data did not differ among the two cohorts. CONCLUSIONS: Significant increase of interstitial lung alterations at [18F]-FDG PET/CT has been demonstrated during the COVID-19 pandemic. Additionally, the incidence curve of imaging abnormalities resulted in resembling the epidemiological data of the general population. These data support the rationale to adopt [18F]-FDG PET/CT as sentinel modality to identify suspicious COVID-19 cases to be referred for additional confirmatory testing. Nuclear medicine physicians and staff should continue active surveillance of interstitial pneumonia findings, especially when new infection peak is expected.

Factors Affecting Mortality in 1022 COVID-19 Patients Referred to an Emergency Department in Bergamo during the Peak of the Pandemic.

The unexpected outbreak of COVID-19 in the area of Bergamo and the general crisis of personnel and devices has been managed as well as possible during the maximum peak of epidemic; Humanitas Gavazzeni Hospital implemented its facilities and organization in order to optimize the treatment of patients. The number of beds in the Intensive Care Unit (ICU) was doubled (from 16 to 33), and more than 220 beds were dedicated to the COVID-19 patients. This paper analyzes the factors affecting mortality in 1022 COVID-19 patients who referred to Humanitas Gavazzeni between February 25 and March 26, 2020. A total of 274 (34.9%) fatal events were registered: 202 among those admitted to the Intensive Care Unit (ICU) and COVID department and 72 among those treated in Acute Admission Unit Level II (AAUl-2) who died before hospital admission. This paper studies 274 dead cases by analyzing patient's characteristics, physiological and laboratory parameters, symptoms, and the scores of severity of the disease. Patients who had fatal events in the AAUL-2 showed the worst parameters of risk. The most important differences regarded the Apache II score, Glasgow Coma Score (GCS), CRP (C-reactive protein), pH, creatinine, RR (respiratory rate), and asthenia.

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.

FDG-PET/CT findings highly suspicious for COVID-19 in an Italian case series of asymptomatic patients.

AIM: To illustrate the [18F]FDG-PET/CT findings in patients affected by cancer with clinical diagnosis of Covid-19 METHODS: We retrospectively reviewed the cases of patients who showed pulmonary involvement unrelated to cancer metastases on March 13 and 16 2020. We reviewed the scans, collected medical history, and exposure information. RESULTS: Among the 13 scans, we identified 5 cases with imaging findings suspicious for viral infection. Peripheral lung consolidations and/or ground-glass opacities in two or more lobes were found. Lung abnormalities displayed increased [18F]FDG uptake (SUVmax 4.3-11.3). All the patients on the day of PET/CT acquisition were asymptomatic, and they did not have fever or cough. In view of the PET/CT findings, home isolation, symptom surveillance, and treatment (in 3/5 patients) were indicated. At 1-week follow-up, 2/5 patients experienced the onset of mild respiratory symptoms. CONCLUSIONS: The [18F]FDG-PET/CT can identify probable Covid-19 disease in the absence or before symptoms onset and can guide patient management. Nuclear medicine staff needs to be aware of the possibility of contact with patients affected by the SARS-CoV-2 infection even if they do not present any symptom. Therefore, safety measures need to be adopted for other patients and hospital staff in order to block the spread of infection.