Severe and mild-moderate SARS-CoV-2 vaccinated patients show different frequencies of IFNγ-releasing cells: An exploratory study.

BACKGROUND: Despite an apparent effective vaccination, some patients are admitted to the hospital after SARS-CoV-2 infection. The role of adaptive immunity in COVID-19 is growing; nonetheless, differences in the spike-specific immune responses between patients requiring or not hospitalization for SARS-CoV-2 infection remains to be evaluated. In this study, we aim to evaluate the spike-specific immune response in patients with mild-moderate or severeSARS-CoV-2 infection, after breakthrough infection following two doses of BNT162b2 mRNA vaccine. METHODS: We included three cohorts of 15 cases which received the two BNT162b2 vaccine doses in previous 4 to 7 months: 1) patients with severe COVID-19; 2) patients with mild-moderate COVID-19 and 3) vaccinated individuals with a negative SARS-CoV-2 molecular pharyngeal swab (healthy subjects). Anti-S1 and anti-S2 specific SARS-CoV-2 IgM and IgG titers were measured through a chemiluminescence immunoassay technology. In addition, the frequencies of IFNγ-releasing cells were measured by ELISpot. RESULTS: The spike-specific IFNγ-releasing cells were significantly lower in severe patients (8 [0; 26] s.f.c.×106), as compared to mild-moderate patients (135 [64; 159] s.f.c.×106; p<0.001) and healthy subjects (103 [50; 188] s.f.c.×106; p<0.001). The anti-Spike protein IgG levels were similar among the three cohorts of cases (p = 0.098). All cases had an IgM titer below the analytic sensitivity of the test. The Receiver Operating Curve analysis indicated the rate of spike-specific IFNγ-releasing cells can discriminate correctly severe COVID-19 and mild-moderate patients (AUC: 0.9289; 95%CI: 0.8376-1.000; p< 0.0001), with a diagnostic specificity of 100% for s.f.c. > 81.2 x 106. CONCLUSIONS: 2-doses vaccinated patients requiring hospitalization for severe COVID-19 show a cellular-mediated immune response lower than mild-moderate or healthy subjects, despite similar antibody titers.

Characteristics of unvaccinated and vaccinated critically ill COVID-19 patients in calabria region (Italy): A retrospective study.

Introduction: After the rapid surge of a novel coronavirus (SARS-CoV-2) in 2020 anti-SARS-CoV-2 vaccines have been developed to prevent the development of critical forms of COVID-19 leading to Intensive Care Unit (ICU) admission. The possibility of ICU admission after the first-cycle vaccination has been already reported; however, no data have been published regarding vaccinated patients with a "booster" dose. This retrospective study describes the characteristics of critically ill patients after the implementation of the regional "booster" dose vaccination program in a southern region of Italy. Materials and methods: We screened all medical records of critically ill COVID-19 patients in the period between January to April 2022. We collected the demographic characteristics, the presence of comorbidities, the vaccination status, the clinical course (arterial blood gases and type of respiratory support) and outcomes (rate of tracheostomy, ICU length of stay and mortality). Results: A total of 272 patients were admitted to ICUs during the study period. 161 patients were unvaccinated, whereas 111 were vaccinated with the complete first-cycle or "booster" dose. The type of respiratory support was similar between groups. Vaccinated patients were characterized by a better oxygenation throughout the whole ICU length of stay. Fourteen unvaccinated and 3 vaccinated patients required tracheostomy (p = 0.045). ICU length of stay was 12.2 (± 7.3) days in unvaccinated patients and 10.4 (± 6.7) days in vaccinated patients (p = 0.036). ICU mortalities were 38.5 and 24.3% in unvaccinated and vaccinated patients, respectively (p = 0.014). Conclusion: Vaccinated patients have better clinical course and outcomes as compared to the unvaccinated population.

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

Ceftriaxone-induced Kounis syndrome in the time of COVID-19

A 53 years old male subject with diabetes mellitus, hypertension, dyslipidaemia, obesity, and history of perianal abscess was admitted to the local hospital for generalized maculopapular rash on his trunk and limbs, which was accompanied by intense itching, sweating, hypotension, and severe chest pain. The rash and the accompanying signs/symptoms appeared 10 min after the administration of ceftriaxone (2 g) as antibiotic therapy for the perianal abscess. The patient had no clinical history for any type of allergy. At the first medical contact, an urgent electrocardiogram was taken showing ST-segment elevation in the anterior–lateral leads. The patient was still then treated with methylprednisolone and adrenalin i.v. as an anaphylactic shock was suspected. Afterwards, the patient was admitted in the emergency department, where he showed flu-like symptoms, chills, and fever. An echo-fast showed left ventricular wall motion abnormalities with hypokinesia of the anterior and posterior wall and moderate mitral regurgitation with normal EF. Laboratory tests showed increased levels of high-sensitivity cTnT (32.8 ng/l;NV < 14), white blood cells (13.74 × 103/μl;NV 5.2–12.4 × 103), IL-6 (10.54 pg/ml;NV < 7), C-reactive protein (PCR) (29.3 mg/l;NV 0–3). As for the cutaneous manifestations, flu-like symptoms, and blood test results (elevation of IL-6 and PCR despite an increase of white cell count) a SARS COV-2 swab was done. As recently noted in several preliminary studies, COVID-19 patients indeed show erythematous rash, and localized or widespread urticaria as initial manifestations in acute severe cases along with the humoural acute-phase response. The latter made it complicated to distinguish viral infection vs. drug administration as the underlying cause of the event. In the meantime, the patient started the treatment for an acute coronary syndrome and acetylsalicylic acid 100 mg, clopidogrel 300 mg orally, and enoxaparin dose subcutaneously were administered. Chest pain disappeared 30 min later and the ECG returned to normal 40 min after drug administration. Subsequently, the swab test result turned to be negative for SARS-CoV-2 and the patient was transferred to our centre for an emergency coronary angiography that revealed proximal subocclusive thrombotic stenosis and middle 70–80% thrombotic stenosis of the left anterior descending (LAD) coronary artery and a 80% thrombotic stenosis of the distal portion of the circumflex. Both vessels’ respective stenoses were treated with PCIs. When considering all together the anamnestic, laboratory, and instrumental/invasive findings, a case of Kounis Syndrome (KS) was suspected. Kounis syndrome (KS) has been indeed defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults mainly elicited by specific medications in male patients. KS involves the following three recognized variants: Type 1: the acute coronary event is secondary to spasm;Type 2: coronary thrombosis is the main culprit, and Type 3: the coronary event occurs secondary to drug-eluting stent thrombosis. Therefore, the patient was finally discharged with the diagnosis of ST-elevated MI likely secondary to a type II KS.