Multiparametric analysis of the specific immune response against SARS-CoV-2.

BACKGROUND: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. OBJECTIVES: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. METHODS: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. RESULTS: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. CONCLUSION: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.

Meropenem population pharmacokinetics and model-based dosing optimisation in patients with serious bacterial infection.

OBJECTIVES: The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target. METHODS: A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment. RESULTS: The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%). CONCLUSIONS: A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.

Fatal Neutropenic Colitis and Clostridium Septicum Bacteremia in a Breast Cancer Patient.

A fatal case of 67-year-old female with metastatic breast cancer on chemotherapy complicated with febrile neutropenia, colitis and sepsis due to Clostridium septicum is presented. Important clinical symptoms, laboratory and radiology findings together with therapy and outcome of neuropenic colitis are also discussed.

Production and use of convalescent plasma in COVID-19 treatment, taking into account the experience in the Central Millitary Hospital Prague.

One of the available treatment alternatives for COVID-19 is the administration of convalescent plasma (CP), blood plasma obtained from people who have undergone the disease. Administration of anti-SARS-CoV-2 antibodies in plasma is a method of passive specific immunization with an expected therapeutic response. CP can also be used for production a specific immunoglobulin. Experience from previous epidemic infections, caused by the coronaviruses SARS-CoV-1 and MERS-CoV, shows that CP contains neutralizing antibodies against the virus, which are probably the main source of its therapeutic potential. However, other immune mechanisms cannot be ruled out, such as antibody-induced cellular cytotoxicity and/or phagocytosis. The use of CP for the treatment of COVID-19 spread during the first half of year 2020 in many countries worldwide and relatively common is also in the Czech Republic, where, at the end of August 2020, about 100 patients were treated with CP. The production and use of CP is governed by the national multidisciplinary guidelines from April 2020 and the recommended therapeutic dose are 2 TU RP (400-450 mL), resp. 4-6 mL/kg. CP is indicated mainly in severe cases of COVID-19, which require oxygen support, ideally within 2-3 days after diagnosis, but our and foreign experience shows a beneficial effect of CP even in moderately severe cases that do not need oxygen treatment.