Lung Ultrasound Findings of Patients with Dengue Infection: A Prospective Observational Study

Lung ultrasound (LUS) is performed for several conditions and is a more sensitive method of detecting pathological pulmonary changes than chest X-ray. Therefore, LUS for individuals with dengue could be an important tool for the early detection of pleural effusions and pulmonary edema signifying capillary plasma leakage, which is the hallmark of severe dengue pathophysiology. We conducted a prospective observational study of pulmonary changes identifiable with LUS in dengue patients admitted to the Hospital for Tropical Diseases in Mahidol University, Bangkok, and the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. The LUS findings were described according to standard criteria, including the presence of A, B1, B2, and C patterns in eight chest regions and the presence of pleural effusions. From November 2017 to April 2018, 50 patients with dengue were included in the study. LUS was performed during the Shonna febrile phase for nine patients (18%) and during the critical-convalescence phase for 41 patients (82%). A total of 33 patients (66%) had at least one abnormality discovered using LUS. Abnormal LUS findings were observed more frequently during the critical-convalescence phase (N = 30/41; 73%) than during the febrile phase (N = 3/9; 33%) (P = 0.047). Abnormal aeration patterns were observed in 31 patients (62%). Only B patterns with only multiple B lines were observed in 21 patients (42%); of these patients, three had already exhibited these during the febrile phase (N = 3). C patterns (N = 10; 24%), pleural effusion (N = 10; 24%), and subpleural abnormalities (N = 11; 27%) were observed only during the critical-convalescence phase. LUS can detect signs of capillary leakage, including interstitial edema and pleural effusions, early during the course of dengue.

Changes in matrix metalloproteinases and their inhibitors in the tears and blood serum of patients with herpetic keratoconjunctivitis under the influence of antiherpetic antibodies and nimesulide

Aim. The aim of the study was to study changes in matrix metalloproteinases and their tissue inhibitors in the tears and blood serum of patients with herpetic keratoconjunctivitis under the influence of antiherpetic antibodies and nimesulide. Materials and methods.65 adult patients with herpetic keratoconjunctivitis (HKC) caused by the herpes simplex virus type 1 (HSV-1) were examined. The etiological diagnosis of HKC was confirmed by polymerase chain reaction. The control group consisted of 32 patients who received basic treatment with acyclovir and interferon in the affected eye. The main group consisted of 33 patients who received antiherpetic immunoglobulin and nimesulide in addition to basic therapy. Immunoglobulin was administered intramuscularly and instilled into the affected eye, and nimesulide was administered orally. The control group consisted of 38 practically healthy adults. Matrix metalloproteinases MMP-1, MMP-8, and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 were determined by solid-phase enzyme immunoassay in the tear fluid and blood serum of patients. The results of the study were processed according to the Student's criterion. Results. With HKC in the affected eye, in the acute phase of the disease, there are: an increase in the concentrations of MMP-1, MMP-8, MMP-9, both in the tear fluid and in the blood serum of patients; a decrease in the concentrations of TIMP-1 and TIMP-2 in the tear fluid, with unchanged levels of these compounds in the blood serum; violation of the balance in the corresponding MMP/TIMP systems to the advantage of MMP. In the convalescence phase, these shifts in the concentrations of MMPs, TIMPs and the balance between them significantly decrease, but their complete normalization does not occur, which is most significant for tear fluid than for the blood serum of convalescents. The combination of antiherpetic immunoglobulin and nimesulide helps to inhibit the exces production of MMP-1, MMP-8, MMP-9 in the lacrimal fluid of the causal eye and in the blood serum of patients, optimizes the level of TIMP-1, TIMP-2 and balance in the corresponding MMPs/TIMPs systems. Conclusion. In the acute phase of SCC, MMPs activity prevails, in the convalescence phase, TIMPs activity prevails. The combination of antiherpetic immunoglobulin and nimesulide has a positive effect on the state of MMPs and TIMPs in the lacrimal fluid of the causal eye and in the blood serum of patients.

Importance of serological testing in the convalescence phase in patients with pulmonary impairment due to COVID 19 - a health care workers analysis

1AbstractSince its discovery, more than 37 million people have been infected by SARS-CoV-2 with deaths around 1 million worldwide. The prevalence is not known because infected individuals may be asymptomatic. In addition, the use of specific diagnostic tests is not always conclusive, raising doubts about the etiology of the disease.The best diagnostic method and the ideal time of collection remains the subject of study. The gold standard for diagnosing COVID 19 is the RT PCR molecular test, usually using an oropharynx and nasopharynx swab. Its sensitivity is 70% and drops significantly after the second week of symptoms. Serological tests, in turn, have increased sensitivity after 14 days, and can contribute to the diagnosis when SARS-CoV-2 infection is suspected, even with negative RT PCR.Our study showed sensitivity and specificity of 100% of the serological test (ELISA method) for cases of viral pneumonia caused by the new coronavirus, suggesting that this test could assist in the diagnosis of pulmonary interstitial changes that have not yet been etiologically clarified. We found a greater immune response in men, regardless of the severity of symptoms. The greater the severity, the higher the levels of IgA and IgG, mainly found in patients with multilobar impairment and in need for oxygen. We concluded that the serological test collected around 30 days after the onset of symptoms is the best diagnostic tool in the convalescence phase, not only for epidemiological purposes, but also for the etiological clarification of pulmonary changes that have not yet been diagnosed.

The influence of recipient SLCO1B1 rs2291075 polymorphism on tacrolimus dose–corrected trough concentration in the early period after liver transplantation

Purpose To explore the relationship between rs2291075 polymorphism in SLCO1B1 gene, which encodes an influx transmembrane protein transporter, and tacrolimus dose–corrected trough concentration (C/D, ng ml−1 mg−1 kg−1) in the early period after liver transplantation. Methods CYP3A5 rs776746 and SLCO1B1 rs2291075 polymorphisms of 210 liver transplantation patients and their corresponding donor livers were assessed by PCR amplification and DNA sequencing. The influence of gene polymorphisms on C/D values of tacrolimus was analyzed. The early postoperative period after liver transplantation was divided into the convalescence phase (1–14 days) and stationary phase (15–28 days) according to the change of liver function and tacrolimus C/D values. Results The combined analysis of donor and recipient CYP3A5 rs776746 could distinguish the metabolic phenotype of tacrolimus into three groups: fast elimination (FE), intermediate elimination (IE), and slow elimination (SE), which was entitled the FIS classification system. Tacrolimus C/D ratios of recipient SLCO1B1 rs2291075 CT and TT carriers were very close and were significantly lower than those of recipient SLCO1B1 rs2291075 CC genotype carriers in convalescence phase (p = 0.0195) and in stationary phase (p = 0.0152). There were no statistically significant differences between tacrolimus C/D ratios of patients carried with SLCO1B1 rs2291075 CT, TT genotype donors, and those carried with SLCO1B1 rs2291075 CC genotype donors. A model consisting of tacrolimus daily dose, total bilirubin, FIS classification, and recipient SLCO1B1 rs2291075 could predict tacrolimus C/D ratios in the convalescence phase by multivariate analysis. However, recipient SLCO1B1 rs2291075 genotype failed to enter forecast model for C/D ratios in stationary phase. Recipient SLCO1B1 rs2291075 genotype had significant effect on tacrolimus C/D ratios in convalescence phase (p = 0.0300) and stationary phase (p = 0.0400) in subgroup, which excluded the interference come from donor and recipient CYP3A5 rs776746. Conclusion SLCO1B1 rs2291075 could be a novel genetic locus associated with tacrolimus metabolism. The combined analysis of donor and recipient CYP3A5 rs776746, recipient SLCO1B1 rs2291075 genotypes, could be helpful to guide the personalized administration of tacrolimus in early period after liver transplantation.

Residual SARS-CoV-2 viral antigens detected in gastrointestinal and hepatic tissues from two recovered COVID-19 patients

Residual SARS-CoV-2 RNA has been detected in stool samples and gastrointestinal tissues during the convalescence phase of COVID-19 infection. This raises concern for persistence of SARS-CoV-2 virus particles and faecal-oral transmissibility in recovered COVID-19 patients. Using multiplex immunohistochemistry, we unexpectedly detected SARS-CoV-2 viral antigens in intestinal and liver tissues, in surgical samples obtained from two patients who recovered from COVID-19. We further validated the presence of virus by RT-PCR and flow cytometry to detect SARS-CoV-2-specific immunity in the tissues. These findings might have important implications in terms of disease management and public health policy regarding transmission of COVID-19 via faecal-oral and iatrogenic routes during the convalescence phase.

Pulmonary function after COVID-19 in early convalescence phase

Pulmonary function after COVID-19 in early convalescence phase. The aim of the study is to investigate the influence of Coronavirus disease 2019 (COVID-19) on pulmonary function in early convalescence phase.Materials and methods. The study included 44 patients (35 male) after COVID-19 without concomitant bronchopulmonary pathology, with a median age of 47.5 years. All patients underwent standard pulmonary function tests (PFTs): spirometry, body plethysmography, diffusion test. Besides, dyspnea on the mMRC scale was assessed, oxygen saturation level (SpO2 ) was measured. Depending on degree of lung damage determined using high-resolution computed tomography (CT), the patients were divided into 2 groups: group 1 (22 patients) — CT 1 and CT 2, group 2 (22 patients) — CT 3 and CT 4.Results. The medians of standard PFTs parameters were in normal values. However, there were statistically significant differences between groups: VC, FVC, FEV1 and TLC were lower in second group. Diffusing capacity was reduced in 52% of patients. Statistical significant correlations were established between lung damage by CT and the parameters of VC, FVC, FEV1 , TLC, IC and DLCO.Conclusion. The degree of functional disorders of lungs depended on the extent of abnormal CT. Impaired diffusing capacity were detected in more than half of the COVID-19 patients in early convalescence phase.

Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

Intranasal Exposure of African Green Monkeys to SARS-CoV-2 Results in Acute Phase Pneumonia With Shedding and Lung Injury Still Present in the Early Convalescence Phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.