Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection.

The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to naïve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

Chikungunya infection in a human immunodeficiency virus-infected kidney transplant recipient returning to Italy from the Dominican Republic.

Since December 2013, chikungunya virus (CHIKV) spread in many countries of the Western Hemisphere, and during the last year some cases of infected European travelers, coming back from the Caribbean, have been reported. The risk of acquiring severe travel-related illness is higher in immunocompromised subjects, such as patients with human immunodeficiency virus (HIV) infection or solid organ transplant recipients. We reported the first case, to our knowledge, of CHIKV infection in an HIV-infected kidney transplant recipient.

Novel multidrug resistant microorganisms in critically ill: a potential threat.

Infections due to multidrug resistant (MDR) pathogens are among the major threats in critically ill patients. Reduced vancomycin susceptibility in Staphylococcus aureus, high-level aminoglycoside resistance in enterococci, extended spectrum beta-lactamase and carbapenemases production in Enterobacteriaceae, carbapenem and colistin resistance in Pseudomonas spp. and Acinetobacter spp. are increasing in many intensive care units around the world. In the last few years some new anti-Gram-positive agents have been developed, whereas for Gram-negatives the available options are very limited. Infections control and antimicrobial stewardship programs are currently the only available options to avoid a further increase of these pathogens.

Pulmonary tuberculosis in an HIV- and hepatitis C virus-coinfected kidney-pancreas transplant recipient: a case report.

Tuberculosis (TB) is a serious infection in immunocompromised patients, such as solid organ transplant recipients and HIV-infected patients. The diagnosis and treatment in this population present several challenges because of the aspecific clinical manifestations, the difficulty in diagnosis, and the choice of the most appropriate therapeutic regimen. Therapeutic challenges arise from drug-related toxicities, interactions between immunosuppressive, antiretroviral, and antituberculous drugs. We present a case of primary TB infection that occurred 3 years after transplantation in a HIV-and hepatitis C virus-coinfected kidney-pancreas recipient. The infection was successfully treated with no hepatotoxicity or rejection with a non-rifampin-containing regimen.

Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.

BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain a major cause of morbidity and mortality. Aspergillus and Candida account for more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30 double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985 and January 1997 were included in the study. RESULTS: Fifty-one patients (41 heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53 invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the most frequent FI in our series accounting for 64.1% (34/53) of all FI [A fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus, n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%) a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8 (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1 (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis. Mortality was 29.4% for patients developing aspergillosis and 33.3% for those experiencing candidiasis. Furthermore, four patients developed the following: one C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp. tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three additional patients were diagnosed affected by deep mould infection by histology alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although their mortality rate is still very high.

Human cytomegalovirus early infection, acute rejection, and major histocompatibility class II expression in transplanted lung. Molecular, immunocytochemical, and histopathologic investigations.

The present study aimed to investigate the relationship between acute rejection and human cytomegalovirus (HCMV) infection, as well as the coexpression of HLA-DR and immediate-early (IE) viral antigens, in 143 transbronchial biopsies and bronchoalveolar lavage fluids of 32 lung transplant recipients. We investigated the occurrence of morphologically overt viral infection with conventional histopathology, the expression of IE antigens with single labeling immunohistochemistry, the coexpression of IE antigens and HLA-DR molecules with double labeling techniques, and the presence of viral IE genes with polymerase chain reaction. Histopathologic study showed overt viral infections (12.6%) in 18 of the 143 biopsies; 8 were in a context of pneumonia and 10 were localizations without surrounding inflammatory cells; immunohistochemistry showed IE viral antigen expression in 31 (21.67%); PCR detected viral IE genes in 73/143 lavage fluids and biopsies (51%). The double labeling immunohistochemical technique showed that most IE antigen-expressing, noncytopathic cells were either HLA-DR negative in areas without infiltrates, or HLA-DR positive in those areas where inflammatory infiltrates were consistent, in the absence of viral cytopathy, with acute rejection. The results indicate that, in transplanted lung, the frequency of morphologically occult HCMV infection (as detected by immunohistochemically and/or PCR) is much higher than that of morphologically overt viral infection. The occurrence of inflammatory infiltrates (consistent with acute rejection) around morphologically occult infected cells and the possible lack of inflammation around both early- and late-infected cells suggest that in biopsies with occult infection the infiltrates should be attributed to allograft reaction. This conclusion would be in keeping with the coexpression of HLA-DR and HCMV IE in infiltrate-rich biopsies that are consistent with acute rejection, as well as with the absence of HLA-DR expression in IE antigen-positive cells in infiltrate-free-areas.