SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality . The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is not fully understood. Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients.

Pharmacological inhibition of the kinin-kallikrein system in severe COVID-19 A proof-of-concept study

Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.

Evolution and epidemic spread of SARS-CoV-2 in Brazil

Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Due to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus transmission and epidemic spread remain challenging. We investigate the impact of NPIs in Brazil using epidemiological, mobility and genomic data. Mobility-driven transmission models for Sao Paulo and Rio de Janeiro cities show that the reproduction number (Rt) reached below 1 following NPIs but slowly increased to values between 1 to 1.3 (1.0-1.6). Genome sequencing of 427 new genomes and analysis of a geographically representative genomic dataset from 21 of the 27 Brazilian states identified >100 international introductions of SARS-CoV-2 in Brazil. We estimate that three clades introduced from Europe emerged between 22 and 27 February 2020, and were already well-established before the implementation of NPIs and travel bans. During this first phase of the epidemic establishment of SARS-CoV-2 in Brazil, we find that the virus spread mostly locally and within-state borders. Despite sharp decreases in national air travel during this period, we detected a 25% increase in the average distance travelled by air passengers during this time period. This coincided with the spread of SARS-CoV-2 from large urban centers to the rest of the country. In conclusion, our results shed light on the role of large and highly connected populated centres in the rapid ignition and establishment of SARS-CoV-2, and provide evidence that current interventions remain insufficient to keep virus transmission under control in Brazil. One Sentence SummaryJoint analysis of genomic, mobility and epidemiological novel data provide unique insight into the spread and transmission of the rapidly evolving epidemic of SARS-CoV-2 in Brazil.

Nosocomial infections among HIV-positive and HIV-negative patients in a Brazilian infectious diseases unit.

BACKGROUND: Some researchers observed that HIV-infected patients have a higher risk of acquiring nosocomial infections (NI). This study compared the incidence of NI among HIV-positive and HIV-negative inpatients. METHODS: Patients from an infectious diseases ward who were classified as positive and negative regarding their HIV status were followed-up for 21 months in a prospective cohort study. Daily surveillance was made with use of Centers for Disease Prevention and Control criteria for NI. RESULTS: NI per 1000 patients-day were 8.16 for HIV-positive patients and 3.94 for HIV-negative patients (P =.01). Central venous catheter (CVC) and urinary catheter utilization was significantly higher among HIV-positive patients than among HIV-negative patients (P <.001). Bloodstream infections (BSI) caused most of the NI, followed by urinary tract infections, vascular infections, and pneumonia. Overall, HIV-positive patients were more likely to have a BSI than were HIV-negative patients (P =.005). When only BSI was analyzed in patients with a CVC, there was no difference in the incidence of BSI between the 2 groups of patients (P =.24). HIV-positive patients were more likely to have an NI caused by Staphylococcus aureus than were HIV-negative patients (P =.04). Other important NI agents in both groups were Acinetobacter baumanii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and coagulase-negative Staphylococcus. CONCLUSIONS: In this study the HIV-positive patients were more likely to have NI than were the HIV-negative patients. Overall, HIV-positive patients are at increased risk for an NI caused either by S aureus or a BSI. Although HIV-positive patients had more CVC-days, there was no difference in the number of BSI among both groups, suggesting that the BSI incidence in the HIV-positive group is not exclusively related to the CVC.

Bacterial meningitis in the elderly: an 8-year review of cases in a University Hospital

The clinical and laboratory characteristics of bacterial meningitis in subjects over 59 years-old were evaluated to establish variables related to prognosis. All patients with clinical and laboratory findings of acute meningitis were included. Sixty-four episodes in 64 patients were registered. S.pneumoniae was responsible for 19 cases (27.5 percent); L.monocytogens - 3; S.aureus -1; S.bovis - 1; S.agalactie - 1 and Corynebacterium jeikeium - 1. Gram negative bacilli caused seven cases; two cases were due to N.meningitidis and one to H.influenzae. In 50 percent of the cases no microorganisms were isolated. The main symptom was fever (67.8 percent). Headache and neck rigidity were absent in about one-half of the cases and the predominant symptoms were psychomotor agitation, stupor or coma. The presence of concomitant diseases, such as diabetes mellitus (26.6 percent) and pneumonia (17.2 percent), were common. The mortality was high (51.5 percent). This poor prognosis was related to L.monocytogens (100 percent), Gram negatives rods (83 percent) and S.pneumoniae (58 percent). The univariate analysis showed that absence of headache (p=0.002), presence of coma (p=0.04), pneumonia (p=0.01) and immunocompromised status (p=0.01) were associated with risk of death. The type of the microorganisms isolated in the elderly patients with meningitis were often unusual ones. The clinical symptoms were minimal and in many cases, the only clinical presentation was change in mental status. Poor prognosis was observed in spite of intensive care. A high index of suspicion for miningitis while caring for elderly with changes in mental status must be maintained to avoid delays in initiating appropriate therapy.

Relative frequency of nosocomial microorganisms at Unicamp University Hospital from 1987 to 1994

Analisa-se a frequencia relativa dos microrganismos isolados das infeccoes hospitalares no Hospital das Clinicas da Unicamp no periodo de 1987 a 1994. O microrganismo mais frequente foi o S. aureus (20,9 por cento), presente nas infeccoes da ferida cirurgica, nas infeccoes da corrente sanguinea e nas arterio-venosas. Nas infeccoes do trato urinario predominaram os bacilos Gram negativos (56,5 por cento) e as leveduras (9 por cento). Foi observado aumento da frequencia de isolados de Acinetobacter baumannii nos ultimos tres anos. Dentre os microrganismos isolados das infeccoes da corrente sanguinea, houve aumento gradual na frequencia de Staphylococcus coagulase negativo e A. baumannii, mas nao houve alteracao na ocorrencia de Candida sp

Molecular typing of Candida albicans strains isolated from nosocomial candidemia

Leveduras do genero Candida tem sido reconhecidas como importantes causadoras de fungemias hospitalares. Foram estudados os DNA cromossomicos de oito cepas de C. albicans, obtidas de oitos pacientes com fungemia hospitalar, por cariotipagem eletroforetica atraves de "pulsed-field gel electrophoresis". As cepas foram obtidas pelo isolamento da levedura em seis hemoculturas e duas infeccoes relacionadas ao uso de cateter intra-venoso central. Foram identificados sete perfis de DNA cromossomico. Dois pacientes mostraram cepas com o mesmo perfil de DNA sugerindo transmissao nosocomial. A cariotipagem eletroforetica revelou excelente capacidade discriminatoria entre os isolados sendo util no estudo das candidemias hospitalares.

Padröes de prescriçöes de antibióticos entre os médicos de um hospital do interior / Prescription patterns of antibiotcs among physicians of the country hospital

O uso abusivo de antibióticos em nosso meio tem sido associado ao aparecimento da multirresistência bacteriana. Traz como pricnipais conseqüências o aumento das infecçöes hospitalares, da duraçäo das mesmas, da freqüência e do tempo de hospitalizaçäo e da mortalidade associada a essas doenças, além da elevaçäo do custo do tratamento. O conhecimento dos padröes de uso de antimicrobianos se torna necessário para a instituiçäo de medidas eficazes que possam atenuar tal problemática. O estudo procura analisar estes padröes em um pequeno hospital do interior do Estado de Säo Paulo

Uso inadequado de antimicrobianos e custos hospitalares: estudo em hospital de pequeno porte no interior de Säo Paulo / Inadequated use of antimicrobial and hospital costs : study in the small hospital in the Säo Paulo

Através da análise da utilizaçäo inadequada de antimicrobianos e seus reflexos nos custos hospitalares de um hospital de pequeno porte do interior do Estado de Säo Paulo, discute-se a importância da existência de atividades de controle de antimicrobianos, para o melhor direcionamento dos gastos hospitalares

Listeriosis and AIDS: case report and literature review

Listeriosis is a not uncommon infection in humans, usually associated with immunodeficient states and with newborns. However, relatively few cases have been reported in HIV-infected patients. This scarcity of reported cases has aroused interest in the association of listeriosis and AIDS. In this paper we present a case of meningitis and septicemia caused by Listeria monocytogenes in a female patient with AIDS. A review of recent medical literature indicates that association of listeriosis and AIDS may be more common than it seems. Recent research in host-parasite interaction in listerial infection suggests an important role for tumor necrosis factor (TNF) and for integralin, a bacterial protein, in modulating listerial disease in AIDS patients. Inadequate diagnosis may be in part responsible for the scarcity of reports

Infecçäo hospitalar em uma enfermaria geral de pediatria / Cross infection in a general pediatric nursery

Estudo prospectivo das infecçöes hospitalares (IH) ocorridas na Enfermaria de Pediatria do HC - UNICAMP, de setembro/86 a dezembro/87. Foram analisadas fichas referentes a 1.187 pacientes. A taxa média de IH foi de 15,2. O sítio de infecçäo mais freqüente foi o respiratório baixo e o germe mais isolado foi o S. aureuas. Dos 124 pacientes que adquiriram IH, 12 evoluiram para óbito pela infecçäo, destes, 83% eram menores que 1 ano de idade e 66% eram desnutridos de III grau

Paracoccidioidomicose e infecçäo pelo vírus da imunodeficiência humana / Paracoccidioidomycosis and infection by the human immunodeficiency virus

Säo apresentados dois casos de paracoccidioidomicose, um em paciente com a síndrome da imunodeficiência adquirida e o outro em paciente com infecçäo pelo HIV. Trata-se dos primeiros relatos em que esta associaçäo é descrita na lieteratura. No primeiro, a micose se evidenciou durante o acompanhamento de paciente com AIDS, que passou a apresentar hépato-esplenomegalia e febre elevada. A ecografia, radiografia simples e tomografia computadorizada do abdomen, demonstraram nódulos sólidos, alguns calcificados, no parênquima esplênico. A punçäo aspirativa da medula óssea confirmou o diagnóstico; o conjunto dos achados caracterizou a forma aguda disseminada da paracoccidioidomicose, a qual levou o paciente ao óbito. No segundo relato, em paciente com infecçäo pelo HIV, a propósito de investigaçäo de tumoraçäo na regiäo inguinal e fossa ilíaca à direita, constatou-se a associaçäo de doença de Hodgkin, tipo celularidade mista e paracoccidioidomicose. Avalia-se a importância destes relatos frente a expansäo da infecçäo pelo HIV e estima-se que mais casos venham a ser relatados em pacientes com AIDS, procedentes de áreas endêmicas desta micose. Propöe-se a inclusäo da paracoccidioídomicose como infecçäo oportunista potencial em pacientes HIV positivos nestas áreas

Efeito adverso no uso intermitente de rifampicina para tratamento de hanseníase / Adverse effect of the intermittent use of rifampicin for leprosy treatment

Os autores apresentam um caso de insuficiência renal aguda, hemólise aguda e trombocitopenia relacionada ao uso intermitente de Rifampicina para tratamento da Hanseníase. Estas reaçöes adversas säo observadas com extrema raridade na literatura mundial. A evoluçäo da paciente foi benina havendo recuperaçäo total da funçäo renal e regressäo completa das alteraçöes hematológicas. Este foi o primeiro registro no Brasil dos efeitos adversos da Rifampicina no tratamento de Hanseníase. Säo discutidos os principais aspectos patogênicos das alteraçöes apresentadas e fe-se revisäo da literatura existente sobre o assunto