The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals.

Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. SIGNIFICANCE: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873.

In Vitro Antimicrobial Susceptibility Profiles of Gram-Positive Anaerobic Cocci Responsible for Human Invasive Infections.

The aim of this multicentre study was to determine the in vitro susceptibility to anti-anaerobic antibiotics of Gram-positive anaerobic cocci (GPAC) isolates responsible for invasive infections in humans. A total of 133 GPAC isolates were collected in nine French hospitals from 2016 to 2020. All strains were identified to the species level (MALDI-TOF mass spectrometry, 16S rRNA sequencing). Minimum inhibitory concentrations (MICs) of amoxicillin, piperacillin, cefotaxime, imipenem, clindamycin, vancomycin, linezolid, moxifloxacin, rifampicin, and metronidazole were determined by the reference agar dilution method. Main erm-like genes were detected by PCR. The 133 GPAC isolates were identified as follows: 10 Anaerococcus spp., 49 Finegoldia magna, 33 Parvimonas micra, 30 Peptoniphilus spp., and 11 Peptostreptococcus anaerobius. All isolates were susceptible to imipenem, vancomycin (except 3 P. micra), linezolid and metronidazole. All isolates were susceptible to amoxicillin and piperacillin, except for P. anaerobius (54% and 45% susceptibility only, respectively). MICs of cefotaxime widely varied while activity of rifampicin, and moxifloxacin was also variable. Concerning clindamycin, 31 were categorized as resistant (22 erm(A) subclass erm(TR), 7 erm(B), 1 both genes and 1 negative for tested erm genes) with MICs from 8 to >32 mg/L. Although GPACs are usually susceptible to drugs commonly used for the treatment of anaerobic infections, antimicrobial susceptibility should be evaluated in vitro.

Systematic Screening of COVID-19 Disease Based on Chest CT and RT-PCR for Cancer Patients Undergoing Radiation Therapy in a Coronavirus French Hotspot.

PURPOSE: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic. METHODS AND MATERIALS: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination. RESULTS: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8). CONCLUSIONS: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Recurrent peritoneal dialysis-related peritonitis caused by Microbacterium resistens.

We report a case of a recurrent peritonitis due to Microbacterium resistens in a 71-year-old male patient undergoing peritoneal dialysis (PD). Importantly, this Gram-positive rod was intrinsically resistant to cephalosporins and vancomycin, classically used in PD-related peritonitis treatment. His infection resolved after several weeks of appropriate therapy (amoxicillin plus gentamicin) and PD catheter removal.