HTLV E INSUFICIÊNCIA RESPIRATÓRIA EM IMIGRANTE PROVENIENTE DO HAITI - RELATO DE CASO

Introdução A infecção pelo vírus linfotrópico de células T humanas (HTLV) é pouco investigada pois a maioria dos pacientes são assintomáticos e não há cura. Apresentaremos o caso de um paciente com leucemia/linfoma de células T adulto (ATLL) associada ao HTLV. Objetivo Destacar a importância de triagem para HTLV e a necessidade de conscientizar sobre sua prevenção. Resultados B.G., 41 anos, masculino, natural do Haiti, residente em Campinas há 11 anos, comissário de bordo. Paciente com histórico de gastrectomia subtotal por estrongiloidíase disseminada 8 anos antes, sem comorbidades, iniciou queixa de mal estar e febre. Em uma semana evoluiu com dispneia, procurando atendimento. Foi internado para oxigenoterapia. Apresentava adenomegalia cervical, axilar, inguinal e mediastinal, além de linfocitose sustentada. Foi descartada Covid-19 e, tendo melhora com tratamento de pneumonia bacteriana, recebeu alta após 15 dias, continuando a investigação ambulatorialmente. Um mês após, apresentava dispneia aos grandes esforços, perda ponderal de 7kg e febre noturna, sendo internado novamente. Tinha células com núcleo multilobulado em sangue periférico (flower cells), infiltrado pulmonar em tomografia, lesões herpéticas em região lombar e verrucosas em genitais. Em biópsia de linfonodo foi feito diagnóstico de ATLL, confirmado em citometria de fluxo de sangue periférico. Sorologia para HTLV positiva e sorologia de HIV negativa. Evoluiu com insuficiência respiratória aguda com necessidade de ventilação mecânica. Teve pesquisa de Pneumocystis positiva no aspirado traqueal. Não respondeu a quimioterapia e zidovudina, falecendo 3 meses após o início do quadro. Conclusão A infecção pelo HTLV é uma doença negligenciada cuja transmissão se dá por via parenteral e sexual. Cerca de 2-5% evoluem para paraparesia espástica tropical e 1-3% para ATLL. Ela também é considerada fator de risco para outras infecções, tais como estrongiloidíase, escabiose, hanseníase e tuberculose. A ATLL é mais frequente em regiões de alta endemicidade, como o Haiti, e particularmente a partir da 4ª década de vida. Apesar da instituição de quimioterapia, apenas 20-40% respondem, com sobrevida média de cinco meses. Associação de zidovudina e interferon-alfa tem sido proposta como possível otimização terapêutica. Por não ser uma infecção de notificação compulsória, não se sabe a real prevalência do HTLV no Brasil. Estudos epidemiológicos para melhor conscientizar sobre propostas de prevenção são importantes, já que, por ora, não há cura.

COVID-19 and invasive fungal coinfections: A case series at a Brazilian referral hospital.

BACKGROUND: COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. METHODOLOGY: A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. RESULTS: During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. CONCLUSION: A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.

Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19.

Background: 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 the accumulation of bradykinin. Methods: In this case control study, 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. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.

Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.