Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

BACKGROUND During the second wave of the coronavirus disease 2019(COVID-19)pandemic,a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extra-pulmonary organ dysfunction.AIM To describe the clinical and laboratory characteristics,outcomes,and management of these patients,and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders.METHODS This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital,between May and August 2021,who fulfilled clearly defined inclusion and exclusion criteria.Outcome was assessed by a change in PaO_(2)/FiO_(2) ratio and levels of inflammatory markers before and after immunomodulation,duration of mechanical ventilation after starting treatment,and survival to discharge.RESULTS Five patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extrapulmonary organ dysfunction at a median interquartile range(IQR)duration of 32(23-35)d after the onset of symptoms.These patients had elevated inflammatory markers,required mechanical ventilation for 13(IQR 10-23)d,and responded to glucocorticoids and/or intravenous immunoglobulin.One patient died(20%).CONCLUSION This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome–Adults by the paucity of extrapulmonary organ involvement.The diagnosis can be considered in patients presenting with delayed respiratory worsening,that is not attributable to cardiac dysfunction,fluid overload or ongoing infections,and associated with an increase in systemic inflammatory markers like C-reactive protein,inteleukin-6 and ferritin.A good response to immunomodulation can be expected.This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus

Background:The appropriate antibiotic treatment for severe scrub typhus,a neglected but widespread reemerging zoonotic infection,is unclear.Methods:In this multicenter,double-blind,randomized,controlled trial,we compared the efficacy of intravenous doxycycline,azithromycin,or a combination of both in treating severe scrub typhus.Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled.The patients were assigned to receive a 7-day course of intravenous doxycycline,azithromycin,or both(combination therapy).The primary outcome was a composite of death from any cause at day 28,persistent complications at day 7,and persistent fever at day 5.

Severe scrub typhus infection: Clinical features, diagnostic challenges and management

Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay(IFA) for the detection of Ig M antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%.

Spectrum of cardiac manifestations and its relationship to outcomes in patients admitted with scrub typhus infection

AIM To study the spectrum of cardiac manifestations in scrub typhus infection and assess its relationship to outcomes.METHODS Demographic data, electrocardiographic(ECG) changes, left ventricular (LV) systolic and diastolic function, myocardial injury (defined as troponin T > 14 pg/mL), and pericardial effusion were documented. Myocarditis was diagnosed when myocardial injury was associated with global LV systolic dysfunction. The relationship between myocarditis and outcomes was assessed using logistic regression analysis and expressed as odds ratio(OR) with 95%CI.RESULTS The cohort(n = 81; 35 males) aged 49.4 ± 16.1 years(mean, SD) presented 8.1 ± 3.1 d after symptom onset. The APACHE-Ⅱ score was 15.7 ± 7.0. Fortyeight (59%) patients were ventilated, and 46 (56%) required vasoactive agents. Mortality was 9.9%. ECG changes were non-specific; sinus tachycardia was the most common finding. Myocardial injury was evident in 61.7% of patients and LV systolic dysfunction in 30.9%. A diagnosis of myocarditis was made in 12.3%. In addition, seven patients with regional wall motion abnormalities had LV systolic dysfunction and elevated cardiac enzymes. Mild diastolic dysfunction was observed in 18 (22%) patients. Mild to moderate pericardial effusion was seen in 51%. On multivariate logistic regression analysis, patients with myocarditis tended to be older (OR = 1.04, 95%CI: 0.99-1.09), had shorter symptom duration (OR = 0.69, 95%CI: 0.49-0.98), and tended to stay longer in hospital(OR = 1.17, 95%CI: 0.98-1.40). Myocarditis was not associated with increased mortality.CONCLUSION In scrub typhus infection, cardiac manifestations are frequent and associated with increased morbidity but not mortality.