The Pfizer-BioNTech BNT162b2 messenger RNA COVID-19 vaccine was found to be highly effective in preventing asymptomatic, symptomatic, and severe SARS-CoV-2 infection.^1-4 Israel was among the first countries to achieve significant nationwide vaccination coverage, leading to rapid containment of SARS-CoV-2 transmission in the community.^5,6 However, resurgence of COVID-19 cases predominated by the Delta variant was observed in June 2021^6,7 and raised concerns about waning immunity of the BNT162b2 vaccine. Declining protection of BNT162b2 against SARS-CoV-2 infection and hospitalization 4 months or more after full vaccination was demonstrated among individuals aged 60 years or older, in which those who completed a 2-dose series in March 2021 had a lower risk of SARS-CoV-2 infection compared with those vaccinated in January 2021.⁷ Similarly, analysis of US data of adults without immunocompromising conditions showed a significant decline in the effectiveness of the BNT162b2 vaccine against COVID-19 hospitalizations, from 91% to 72% more than 120 days after completion of vaccination.⁸ These findings are consistent with data showing time-dependent reduction in neutralizing antibody titers after vaccination.^9,10

Introduction: C-reactive protein (CRP) is a marker commonly used in clinical practice as a reference for the inflammatory activity in vivo. Low levels are often associated with good health and lower risk for adverse outcomes. Patients and methods: We examined medical records of the last 6 years, of all patients admitted for hospitalization in internal medicine wards who had the first CRP measurement below ≤ 0.03 mg/L (detection limit). Diagnosis criteria and 7 days’ survival were reviewed. Results: Out of 61,590 total admissions to internal medicine wards, three hundred and thirteen patients had CRP equal to or lower than 0.03 mg/L (0.5%). Second CRP measurement revealed gradual increment up to 10.8 ± 35.4 mg/L. Four patients died within 7 days from admission. Discussion: Presentation to the internal medicine department with a very low concentration of CRP is highly unusual, but it does not exclude the existence of significant acute morbidities. Clinicians should take additional CRP tests before any conclusion is considered regarding the presence or absence of an inflammatory response.

Background: Several biomarkers and models have been proposed to predict in-hospital mortality among COVID-19 patients. However, these studies have not examined the association in sub-populations. The present study aimed to identify the association between the two most common inflammatory biomarkers in the emergency department and in-hospital mortality in subgroups of patients. Methods: A historical cohort study of adult patients who were admitted to acute-care hospital between March and December 2020 and had a diagnosis of COVID-19 infection. Data on age, sex, Charlson comorbidity index, white blood cell (WBC) count, C-reactive protein (CRP), and in-hospital mortality were collected. Discrimination ability of each biomarker was observed and the CHAID method was used to identify the association in subgroups of patients. Results: Overall, 762 patients (median age 70.9 years, 59.7% males) were included in the study. Of them, 25.1% died during hospitalization. In-hospital mortality was associated with higher CRP (median 138 mg/L vs. 85 mg/L, p < 0.001), higher WBC count (median 8.5 vs. 6.6 K/µL, p < 0.001), and higher neutrophil-to-lymphocyte ratio (NLR) (median 9.2 vs. 5.4, p < 0.001). The area under the ROC curve was similar among all biomarkers (WBC 0.643, NLR 0.677, CRP 0.646, p > 0.1 for all comparisons). The CHAID method revealed that WBC count was associated with in-hospital mortality in patients aged 43.1–66.0 years (8: 43.3%), and CRP in patients aged 80.1+ years (≤47 mg/L: 18.8%, 47.1–149 mg/L: 43.1%, and 149.1+: 71.7% mortality). Conclusions: WBC, NLR, and CRP present similar discrimination abilities. However, each biomarker should be considered as a predictor for in-hospital mortality in different age groups.

Patients with lymphoproliferative diseases are at high risk for SARS‐CoV‐2‐related complications and mortality. The role of casirivimab and imdevimab (REGEN‐COV), a neutralizing antibody cocktail, to treat immunocompromised hemato‐oncological patients with SARS‐CoV‐2 disease 2019 (Covid‐19) remains unknown. Here, we present our clinical experience on the outcome of 15 hematological patients treated with REGEN‐COV for SARS‐CoV‐2 infection. Most patients failed to respond or achieved low antibody titer after 2–3 doses of BNT162b2 mRNA vaccine. All patients experienced clinical improvement with no mortality within a median follow‐up of 70 days. In conclusion, early administration of REGEN‐COV to high‐risk hematological patients may prevent clinical deterioration and mortality from SARS‐CoV‐2 infection. The effectiveness of neutralizing antibodies may vary depending on the virus variants and in particular with the omicron variant (B.1.1.529).

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new “inflammatory stamp”.