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BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant S. aureus (VRSA) frequently cause nosocomial infections yearly. During the COVID-19 pandemic, the potential for excessive use of antibiotics is a global threat to the increasing incidence of multiresistant bacteria. AIM: This study aimed to determine MRSA and VRSA colonization and identify factors associated with the risk of MRSA and VRSA nasal colonization in health workers at Dr. Soemarno Sosroatmodjo General Hospital, Kuala Kapuas, as one of the type C hospitals in Indonesia. METHOD(S): This cross-sectional analytic study at Dr. Soemarno Sosroatmodjo General Hospital, a tertiary hospital in Indonesia. A 128 health workers' subjects had undergone nasal swab screening for MRSA and VRSA colonization examinations. Then, they were asked to complete a questionnaire concerning the risk factors of MRSA and VRSA infections. RESULT(S): Nasal swab results obtained as many as 30 (23.5%) MRSA positive subjects and 6 (4.7%) subjects with positive VRSA. The most common risk factors that led to MRSA colonization included a history of positive MRSA in the previous hospital (60%), a history of ear, nose, and throat infection (41.7%), and did not do hand rub/handwash (36.7%). In comparison, the most risk factors for VRSA colonization were having pigs farm at home (33.3%), a history of positive MRSA in the previous hospital (20%), and a history of hospitalization in the past 6-12 months (16.7%). The results of multivariate analysis showed the most powerful and statistically significant risk factors in influencing nasal MRSA colonization were a history of positive MRSA in the previous hospital (OR 13.69, 95% confidence intervals [CI]: 1.34-140.25, p = 0.028) and did not do hand rub/handwash (OR 2.95, 95% CI: 1.167-7.49, p = 0.023). Meanwhile, marital status (OR 0.160, 95% CI: 0.02-1.06), p = 0.058) and home care service (OR 6.10, 95% CI: 0.79-46.96, p = 0.082) were the strongest risk factors for nasal colonization of VRSA but not statistically significant. CONCLUSION(S): As many as, 23.5% and 4.7% of healthcare workers' subjects were found with nasal colonization of MRSA and VRSA, respectively. Accordingly, strict policies are needed to minimize the transmission of these organisms from the hospital setting to the community.Copyright © 2023 Siti Nur Rohmah, Rizka Humardewayanti Asdie, Ida Yosopa, Daya Daryadijaya.
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Aim. To determine the clinical efficacy and safety of the immobilized (sorbed) probiotics Bifidobacterium bifidum 1 (5x108 CFU) and B. bifidum 1 (5x107 CFU) in combination with Lactobacillus plantarum 8P-A3 (5x107 CFU) in the complex therapy of pneumonia caused by SARS-CoV-2 in adult patients without severe risk factors and their impact on health-related quality of life (QoL). Material and methods. An open, randomized prospective study included 100 patients (45 males, 55 females), aged from18 to 60 years without risk factors for severe COVID-19, with pneumonia confirmed by computed tomography and an area of lung lesion no more than 75% (moderate forms). SARS-CoV-2 RNA in nasal and oropharyngeal swabs (RT-PCR) was detected in 72% of the participants, in the rest it was highiy probable in terms of the aggregate parameters. The publication presents the results of self-assessment (94 respondents) of working capacity limitations, shortness of breath, intestinal disorders since the end of the probiotic regimen (PR: hospitalization period - B. bifidum 1, 3 capsules 2 times a day for 10 days, then after hospitalization - B. bifidum 1 in combination with L. plantarum 8P-A3 2 powders 3 times a day for 14 days) and QoL (Short Form Medical Outcomes Study: SF-36) 1 month after hospitalization. Results. At the end of PR, the ability to engage in daily activities was higher by 23.1% [95% confidence interval 5.3-37.3, OR 0.08 (0.08-0.77)]. Difficulty of breathing during exercise was less common by 29.7% [15.1-44.5%], OR 0.09 [0.02-0.40], hard stools and no bowel movements were recorded less often by 21.3% [8.5-34, 1] for 1-3 days. One month after hospitalization, the QoL of the patients receiving standard treatment was significantly reduced relative to population indicators in Russia. It was more significantly due to the psychological component of health [total measurement 38.1 (36.2-40.0)] and less significantly due to the physical component [49.5 (48.3-50.8)]. The main reasons limiting daily activities [Role Emotional (RE): 39.4 (37.4-41.4)] were decreased vitality [VT: 40.2 (38.9-041.5)], emotional depression [Mental Health (MH): 41.2 (39.4-43.0)], deficit of social contacts [Social Functioning (SF): 45.1 (43.7-46.6)]. The patients who received PR had a higher ability to carry out daily activities [RE: 57.7 (55.6-59.7)], the severity of psychological problems associated with fatigue, anxiety and depression was lower [MH: 59.8 (58.7-60.9), p<0,001]. The effect of the PR on negative perceptions of social isolation was comparatively less [SF: 53.9 (52.2-55.4)]. The QoL of the patients who additionally suffered from diarrhea in the acute period of SARS-CoV-2 pneumonia was worse in comparison with the patients without diarrhea (due to pain and inability to endure physical activity). The effects of immobilized (sorbed) probiotics to the QoL of the patients with diarrhea during the acute period of COVID-19 were most significant. Conclusion. PR had a significant positive effect on the QoL within a month after hospitalization, increasing working capacity and improving mental health, reducing the severity of psychological problems and fatigue. Additional researches are needed on the possible relationship of organic and functional gastrointestinal diseases with the progression of diarrhea in patients infected with SARS-CoV-2. No side effects of the sorbed probiotics regimen have been identified.Copyright © Eco-Vector, 2022.
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Intro: In Australia, the main methods to diagnose COVID-19 are through rapid antigen tests (RATs) and through nucleic acid amplification testing (NAAT, including polymerase chain reaction) on healthcare worker (HCW)-collected combined nose/throat swabs. With self-collection widely used by the public for RATs, the aim of this study was to evaluate the performance of self-collected samples using commercial NAAT for SARS-CoV-2. Method(s): Consenting participants aged 14 years and older were provided with a self-collection pack containing instructions and either a FLOQSwab (Copan) or a Rhinoswab (Rhinomed). Participants collected their own nasal sample unsupervised prior to having a HCW-collected combined nose and throat swab taken for standard of care NAAT. Paired self-collected and HCW samples were tested on the cobas SARS-CoV-2 assay (Roche) and the Aptima SARS-CoV-2 assay (Hologic). Finding(s): We demonstrated comparable sensitivity, specificity, and agreement between self-collected nasal and Rhinoswab samples, compared to HCW- collected samples tested using the cobas SARS-CoV-2 and Aptima SARS-CoV-2 assays. In our study the clinical performance of self-collected specimens was comparable to HCW-collected samples, with both self-collect nasal and Rhinoswab samples resulting in 90-95% sensitivity, and in most cases >95% specificity. Discussion(s): Without the availability of samples for NAAT the ability to perform genomic testing is limited, reducing surveillance and public health investigations. We showed that genomic sequencing from self-collected samples can correctly identify the virus lineage and that the main determination of successful genomic testing is a high viral load rather than collection method. Conclusion(s): These data support self-collection as an accessible method for community testing for COVID-19 and introduces a novel collection device, the Rhinoswab as an alternative to the standard nasal swab. The testing method of self-collection can be expanded from the widely used RATs to NAAT and genomic testing which may inform the management and public health response to the COVID-19 pandemic.Copyright © 2023
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Intro: The number of PCR-confirmed cases may serve poorly as a surveillance data for a representative disease activity, due to its bias towards symptomatic cases or people having an identifiable risk exposure, and the high dependency on changing testing policy. We reported a large-scale ad-hoc community surveillance initiative, Daily Antigen Rapid Testing Surveillance (DARTS) System, using self-performed rapid antigen tests(RAT). Method(s): A representative cohort of 10000+ individuals was enrolled over the territory. Participants were divided into 7 sub-cohorts to achieve a rolling schedule with 1400+ individuals on a daily basis. Participant performed the RAT regularly irrespective of symptom or exposure history, with a self-sampled throat-and-nasal swab. RAT result and photo were reported on the same day of testing through an online platform. Daily point prevalence was disseminated on a real-time dashboard to inform the situation awareness(https://covid19.sph.hku.hk/dashboard). Finding(s): Since its launch during the peak of the fifth wave in March 2022, the system has tracked the changing trajectory of different phases of the Omicron pandemic, including the rapidly subsiding daily prevalence from an initial high value of 12.7% (8.4-18.7) in early March to a baseline of 0.6% (0.2-1.4) in early April, maintained with a non-zero baseline (0.1-0.3%) over May, and subsequent stepwise increase to 0.5% (0.2-1.2) in June. The reproduction number increased from 0.66(0.63,0.70) to 1.23(1.14,1.33) from March to June, signifying the gradual increase of residual Omicron transmission. Conclusion(s): Our DARTS system has demonstrated the feasibility of a participatory surveillance system using self-performed RAT, and its utility as an ad-hoc surveillance to timely reflect the rapidly changing epidemic trajectory. Regular testing irrespective of symptom and exposure risk helps to give more representative picture, including subclinical cases who also carried an implication of disease transmission. The use of RAT also helps to avoid the constraint of manpower and testing capacity, and has been quickly adopted for case definition.Copyright © 2023
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The global pandemic of coronavirus infection (COVID-19) has set complex diagnostic tasks for doctors of polyclinics and hospitals. Considering the simultaneous pandemic spread of two infectious diseases - COVID-19 and HIV infection, the problem of studying the clinical features of combined COVID-19/HIV infection becomes urgent. The aim of the study was to determine the features of the diagnosis and course of COVID-19 against the background of HIV infection in patients undergoing inpatient treatment. Material and methods. The study was conducted on the basis of the temporary Clinical Medical Center COVID-19 of the A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation in Moscow from October 2020 to January 2022. The study included 31 233 patients with COVID-19 complicated by pneumonia. To analyze the features of the course of combined COVID-19/HIV infection, a group of 51 HIV-infected patients was identified. The diagnosis of COVID-19 was determined based on the detection of SARS-CoV-2 RNA by PCR in nasal/oropharyngeal smears and/or according to computed tomography of the lungs (CT). During the study, age, gender, anamnesis, objective examination data were analyzed, taking into account the results of CT scans of the chest organs, data from routine laboratory blood tests, oxygen support regimens, treatment outcomes and duration of detection of SARS-CoV-2 RNA. All patients were treated according to the Temporary Clinical Guidelines for the Diagnosis and Treatment of COVID-19, 14 version dated 12/27/2021. Results. The number of patients with combined HIV infection and SARS-CoV-2 out of the total number of hospitalized COVID-19 patients (n=31 233) was 0.16%. Upon admission, 30 (59%) patients reported having HIV infection and receiving antiretroviral therapy (ART). HIV infection was first diagnosed in 21 patients at 2-3 weeks of inpatient treatment. The average age of patients with SARS-Cov-2/HIV co-infection was 1.5 times less than in patients without HIV (41.1+/-5.3 and 64.4+/-10.1, respectively) (p<=0.05). Concomitant pathology (hypertension, type 2 diabetes mellitus, chronic kidney disease and chronic lung diseases) was less common (51%) in the group of combined infection than in the group without HIV (83%). However, in 41% of patients with coinfection, chronic viral hepatitis B, C was detected, in contrast to 0.3% of cases of COVID-19 patients without HIV. 26 (51%) patients were discharged with improvement, while the average bed-day did not differ from patients without HIV infection (13.4+/-4.5 days and 11.7+/-5.2, respectively) (p>=0.05). 7 (24%) patients at the time of discharge (16.8+/-4.2 days) with clinical and laboratory improvement maintained a positive result of PCR RNA on SARS-Cov-2. In 22 (43%) patients with coinfection, hospitalization was fatal for 3 to 21 days of treatment, with ARDS with respiratory and multiple organ failure, which is 3.6 times higher than in patients without HIV infection. The analysis showed that, regardless of the result of PCR on SARS-CoV-2 RNA, in non-specialized hospitals, HIV testing is indicated for young patients with fever for more than 14 days, with lung damage in the form of bilateral interstitial changes according to CT, a history of chronic hepatitis C, B, with progressive severity of the condition on against the background of COVID-19 therapy. Early consultation of an infectious disease specialist, examination of sputum/lavage by PCR for pathogens of opportunistic infections and the appointment of ART and drugs for the treatment of opportunistic diseases will improve the quality of medical care for patients in a non-core HIV hospital will improve the prognosis of COVID-19.Copyright © Eco-Vector, 2022.
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Background: Despite increased social vulnerability and barriers to care, there has been a paucity of data on SARS-CoV-2 incidence among key populations in sub-Saharan Africa. We seek to characterize active infections and define transmission dynamics of SARS-CoV-2 among people who inject drugs (PWID) and their sexual and injecting partners from Nairobi and the coastal region in Kenya. Method(s): This was a nested cross-sectional study of SARS-CoV-2 infection from April to July 2021 within a cohort study of assisted partner services for PWID in Kenya. A total of 1000 PWID and their partners (500 living with and 500 living without HIV) were recruited for SARS-CoV-2 antibody testing, of whom 440 were randomly selected to provide self-collected nasal swabs for real-time PCR testing. Whole genome sequencing (WGS) was completed on a limited subset of samples (N=23) with cycle threshold values 32.0. Phylogenetic tree construction and analysis was performed using the Nextstrain pipeline and compared with publicly available SARS-CoV-2 sequences from GenBank. Result(s): A total of 438 (99.5%) participants provided samples for SARS-CoV-2 PCR testing. Median age was 37 (IQR 32-42);128 (29.2%) were female;and 222 (50.7%) were living with HIV. The overall prevalence of SARS-CoV-2 infection identified by RT-PCR was 86 (19.6%). In univariate analyses, there was no increased relative risk of SARSCoV- 2 infection related to positive HIV status, frequenting an injection den, methadone treatment, unstable housing, report of any high-risk exposure, or having a sexual or injecting partner diagnosed with COVID-19 or who died from COVID-19 or flu-like illness. Eight samples were successfully sequenced via WGS and classified as WHO variants of concern: 3 Delta, 3 Alpha, and 2 Beta. Seven were classified into clades predominantly circulating in Kenya during 2021. Notably, two sequences were identical and matched identically to another Kenyan sequence, which is consistent with, though not indictive of, a transmission linkage. Conclusion(s): Overall, the risk of SARS-CoV-2 infection in this population of PWID and their partners was not significantly associated with risk factors related to injection drug use. At a genomic level, the SARS-CoV-2 strains in this study were consistent with contemporary Kenyan lineages circulating during the time and not unique to PWID. Prevention efforts, therefore, must also focus on marginalized groups for control given the substantial amount of mixing that likely occurs between populations.
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Background: The tolerability of mRNA COVID-19 vaccines among people living with HIV (PLWH) has been understudied in vaccine trials. CoVPN 3008 (Ubuntu) is the largest multicenter Phase 3 efficacy trial of mRNA vaccines in sub-Saharan Africa. Method(s): We enrolled adults age >=18 years living with HIV or another comorbidity associated with severe COVID-19. Previously vaccinated individuals were excluded. Baseline testing included HIV, CD4 count and HIV viral load (VL) (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 nucleic acid amplification test (NAAT). All participants receive vaccinations at months 0 and 6, and SARS-CoV-2 seronegative individuals also receive vaccination at month 1. This analysis includes mRNA-1273 vaccinations at months 0 and 1. Reactogenicity (solicited adverse events [AEs]) was assessed among a representative subset of participants (Safety Subset, SS) for 7 days post-vaccination. Baseline characteristics associated with moderate/severe reactogenicity events were assessed by univariate and multivariate logistic regression. Result(s): 14002 participants were enrolled in the trial (1510 into the SS) at 46 sites from 2 Dec 2021 to 9 Sep 2022. At baseline in the SS, 71% (1065) were female, median age 38 years (IQR 32-46), and median BMI 25.0 (IQR 20.7-30.2). 73% (1108) were SARS-CoV-2 seropositive, and 8.7% (131) had a positive nasal NAAT swab. 16% (197) had a history of tuberculosis. 84% (1267) were PLWH, with median CD4 count of 614 cells/muL (IQR 414-861);7.8% had CD4 count < 200. 21% (238) had detectable HIV VL (>=50 copies/mL), with median VL 1660 (IQR 182-23932). 14% (172/1262) and 12% (64/542) of PLWH reported moderate/severe reactogenicity after the 1st and 2nd vaccination (Figure), with no hospitalizations. Female PLWH and CD4 count >500 had 35% (p=0.03) and 44% (p=0.04) increased odds of moderate/severe reactogenicity, respectively. Other baseline characteristics were not associated with the odds of reporting moderate/severe reactogenicity among PLWH after 1st vaccination. Similar trends were seen after the 2nd vaccination, but none reached statistical significance. In multivariate models, female sex remained associated with increased odds of moderate/severe reactogenicity after the 2nd vaccination. Conclusion(s): Similar to observations in HIV-negative populations, mRNA-1273 was well tolerated by PLWH with more reactogenicity in females. Impaired inflammatory responses among participants with CD4 counts < 500 cell/muL may explain less moderate/severe reactions.
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Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.Copyright © 2023, Indian Academy of Pediatrics.
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The pandemic of coronavirus infection is characterized by a low percentage of complications and severe forms in sick children compared to the adult population. However, there have been described cases of severe clinical course of COVID-19 in children with comorbidities among which is obesity. The aim of this study was to analyze the severe course of a new coronavirus infection paralleled with morbid obesity in a pediatric patient. Materials and methods. All accompanying patient medical documentation was examined. Results and discussion. From the anamnesis of life it is known that the patient was long time complained of intensively increased body weight, on which she repeatedly underwent examinations. In 2018, hypothalamic pubertal syndrome was diagnosed for the first time, for which the patient received hypoglycemic and antihypertensive drugs, hepatoprotectors on an ongoing basis. In the epidemiological anamnesis, the intrafamilial COVID-19 contact with mother was established. The main disease began acutely with a rise in body temperature up to 39-39.5degreeC, cough and weakness. During the first week of illness, the patient did not seek medical help and receive self-treatment, but the positive effect was not achieved. Saturation measurement showed low oxygen level (SpO2 71%). In this regard, the patient underwent chest computed tomography, which revealed a bilateral interstitial polysegmental lung lesion with signs of consolidation. After emergency hospitalization, the patient was prescribed empiric antibiotic therapy, anti-inflammatory and antithrombotic treatment, as well as respiratory support. A positive PCR result of a throat and nasal swab for SARS-CoV-2 was obtained in the hospital. Due to a poor response to therapy, the patient was transferred to a respiratory hospital. At the time of hospitalization, the condition was considered severe due to severe respiratory failure and premorbidity. The range of treatments included oxygenotherapy, antibacterial and anticoagulation therapy, as well as surfactant and the nucleoside analogue Remdesivir. During treatment, the clinical picture gained a positive trend, and after 6 days of hospitalization the patient no longer needed respiratory support. According to the results of repeated computed tomography, bilateral interstitial polysegmental pneumonia was diagnosed with damage to the lung tissue up to 95%. The patient remained stable and showed no signs of respiratory failure during the following days of hospitalization. On the 20th day of ilness, the patient was discharged from hospital with full clinical recovery. Conclusion. This clinical case demonstrates the role of premorbid background in aggravating the clinical picture of a new coronavirus infection in a child. Careful study of anamnestic characteristics is necessary in patients of any age, even with an uncomplicated disease course.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.
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Introduction: ICU survivors may present symptoms of acute stress disorder(ASD) or post traumatic stress disorder (PTSD) [1], as defined by the Diagnostic and Statistical Manual of Mental Disorders. Prevalence of PTSD in ARDS affects 20% of survivors but is higher in SARS/ MERS patients [2];risk factors are delirium, ICU sedation, altered memories or ICU amnesia [3]. Method(s): We enrolled patients discharged from our ICU (Pavia-Italy) after admission for acute respiratory failure due to COVID-19. Written consent was collected. Inclusion criteria: age >= 18 years, ICU admission between February 2020 and July 2021 for severe COVID-19, SARSCoV-2 infection confirmed by positive nasal swab/tracheal aspirate, available follow-up visit. Exclusion criteria: refuse to attend the follow up visit, refuse to perform the psychological tests. To assess ASD/ PTSD we used the IES-R: a total mean score >= 33 was the cut-off value for ASD/PTSD;subscale scores for avoidance, intrusion, hyperarousal were calculated. Quantitative and categorical variables are expressed as median [IQR] and number (%). Result(s): Of the 491 patients admitted to ICU, 113 patients were included (males 84(74.3%), age 61.0[52.0-66.0] years, BMI 28.2[25.8- 31.6] kg/m2, SAPS2 31.0[26.0-41.5], ICU stay 17.0[8.0-28.0] days, invasive mechanical ventilation 61(54.0%). They were assessed in median 107.0 [82.0-150.0] days after ICU discharge. 37 patients (32.7%) had ASD/PTSD, higher than the expected 20% in general ARDS population (p < 0.001). Both intrusion 11.0[5.0-17.0] and avoidance 7.0[3.0-13.0] median scores were higher than hyperarousal 5.0[2.0-9.0]. Conclusion(s): ASD/PTSD is frequent after discharge to ICU for severe COVID-19, this prevalence is higher than other ARDS population, maybe for stigma, difficulties with quarantine and isolation. Patients have higher intrusion and avoidance scores, maybe because during the pandemic isolation was unavoidable.
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Background: Jails house vulnerable persons. Crowded conditions, restricted access to medical care, and limited resources facilitate infectious disease outbreaks, particularly for airborne, highly transmissible diseases like COVID-19 (C19). Wastewater-Based Surveillance (WBS) is a low-cost, highly sensitive, non-invasive method that can provide an early warning of C19 surges in communities. We examined the value of SARS-CoV-2 WBS for a mega-jail. Method(s): 28-week study period: 10/20/21- 5/5/22. Wastewater samples were collected x 25 weeks;SARS-CoV-2 RNA was measured using RT-qPCR. We sampled one manhole serving multiple housing units. C19 rapid test data on jail entrants were summarized daily by the jail;16 mass PCR screenings using selfcollected nasal swabs were conducted by the study team. Individual diagnostic tests were collated and analyzed on a weekly basis. Data were summarized by % of the tested jailed individuals found infected. The Spearman correlation coefficient between weekly SARS-CoV-2 RNA in wastewater and % of positive (pos) C19 diagnostic tests were calculated;we also used linear regression to assess the predictability between paired Ct values and weekly % of pos diagnostic tests. Result(s): Weekly WBS coupled with periodic mass testing of jailed individuals was feasible. The efficiency of gathering individual nasal swabs increased to 3 tests collected per minute through a CQI process. PCR signal strength for SARSCoV- 2 RNA in jail wastewater correlated with the % of jail residents tested who had C19. The mean RT-qPCR Cycle threshold (Ct) value was 35.2. Overall, 3.4% of nasal swabs were pos. A strong inverse correlation was observed between % nasal swab pos and WBS Ct value (Figure.) The Spearman correlation coefficient was r= 0.628;linear regression likewise showed a similar correlation. Conclusion(s): Weekly WBS results for C19 correlated with the proportion of C19 individual test results. WBS proved to be a practical strategy to surveil for C19 in this jail setting. We are developing means to identify exact source, by housing unit, of wastewater with positive signal. Future studies will explore WBS for Mpox and HIV in correctional facilities. HIV RNA can be found in wastewater specimens;whether WBS for HIV in congregate facilities is feasible remains an open question.
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From March 2020 to May 2022, when SARS-CoV2 pandemic started spreading in Italy, 15 consecutive patients with non-Hodgkin Lymphoma (NHL) have been treated at the Pediatric Unit of Fondazione IRCCS Istituto Nazionale dei Tumori. Three of 15 patients developed COVID19 while on treatment [1 Burkitt lymphoma (BL), 1 anaplastic large cell lymphoma, 1 lymphoblastic T-cell lymphoma (T-LL)] and one patient at diagnosis [gray zone lymphoma (GZL), previously misdiagnosed as Hodgkin lymphoma]. Median age at diagnosis was 12 years;3 were male. Median positivity time of the nasal swab was 58 days (range 9-107 days). All patients remained asymptomatic or paucisymptomatic (flu-like symptoms) while positive. The first positive patient with T-LL, was in the induction phase of the Euro-LB-02 protocol guidelines: he succeeded in completing the whole treatment during the 107 days of swab positivity, experiencing mild toxicities (grade 2 transaminases and grade 3 lipase increase, both reversible) without significant delays. For this reason, we reduced the total dose of the first HD-MTX (protocol M) and administer the subsequent doses in 6 hours infusion instead of 24 with no further toxicities. After this first experience, all the subsequent patients have been treated accordingly, without major deviations from the established protocols. Minor precautions: the patient with refractory GZL received IEP course instead of IGEV as second-line treatment to avoid severe subsequent immunosuppression;the patient with BL omitted the fourth course of Rituximab during the period of swab positivity. Overall, we did not observe outstanding toxicities except for a toxic MTX level with subsequent reversible acute renal failure. Main teaching from these pilot experiences, which may translate into guidelines: 1) SARS-CoV2 infection is not an absolute contraindication to the oncological treatments. This is of main importance for the patients affected by lymphoma whose dose-intensity has a prognostic value. 2)We need to pay caution during HD-MTX treatment;indeed, we observed unexpected similar toxicities in other patients treated with HD-MTX for other solid malignancies. 3) The clearance of SARS-CoV2 might be exceptionally prolonged with persistent positivity of the nasal swabs for a longer time than the matched healthy population due to the immunosuppression characterizing lymphoma patients. For this reason and given the importance of maintaining the dose-intensity, specific treatments aiming at speeding up the clearing process are warmly suggested. (Figure Presented) Figure 1: (: 091) ITHACA study design and blood sampling time points. (OHT = Orthotopic Heart Transplant).Copyright © 2022 Elsevier Ltd. All rights reserved.
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Background: Individuals living with HIV are at increased risk of morbidity and mortality from COVID-19. Furthermore, SARS-CoV-2 infection in immunocompromised HIV infected individuals poses a risk to prolonged infection and viral shedding and the emergence of new variants of concern (VOCs). Using the SIV macaque model for AIDS, we are investigating the hypothesis that immune dysfunction during HIV infection will prolong SARSCoV- 2 viral infection, promote enhanced COVID-19 disease, and accelerate viral evolution. Here, we report the impact of SIV-CoV-2 co-infection on immune responses and pathogenesis. Method(s): Eight female rhesus macaques (aged 7-15 years, 5.5-9.9kg) were infected with SIVmac251 via low dose intravaginal challenge and then inoculated with 6.5x105 TCID50/mL SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV infection via combined intranasal and intratracheal routes. Blood, bronchoalveolar lavage (BAL), stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI) to measure immune responses and viremia. ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Result(s): Three days post-SARS-CoV-2 infection, we observed a transient decrease in CD4 counts, but there were no changes in clinical symptoms or plasma SIV viral loads. However, SARS-CoV-2 replication persisted in the upper respiratory tract, but not the lower respiratory tract. In addition, SARS-CoV-2 IgG seroconversion was delayed and antigen-specific T-cell responses were dampened. Notably, viral RNA levels in nasal swabs were significantly higher 7-14 DPI in SIV+ compared to previously published results using the same SARS-CoV-2 challenge virus in SIV- rhesus (PMCID: PMC8462335, PMC8829873). In addition, SIV/CoV-2 co-infected animals exhibited elevated levels of myeloperoxidase (MPO), a marker of neutrophil activation and increased lung inflammation. Conclusion(s): Here we provide evidence for the utility of the rhesus macaque in modeling human HIV-SARS-CoV-2 co-infection. Our results suggest that immunosuppression during SIV infection impairs de novo generation of anti-SARS-CoV-2 immunity, that may contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine if SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques.
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Background: Rebound of SARS-CoV-2 RNA and symptoms has been reported in people treated with nirmatrelvir/ritonavir. Since the natural course of viral and symptom trajectories during COVID-19 have not been well described, we evaluated the incidence of viral rebound and symptom relapse in untreated individuals with mild-to-moderate COVID-19. Method(s): This analysis included 563 participants randomized to placebo in the ACTIV-2/A5401 platform trial. Participants recorded the severity (scored as 0-3) of each of 13 targeted symptoms daily from days 0-28, with symptom score being the summed score (0-39). Symptom rebound was defined as >=4 point increase in symptom score between the maximum and the preceding minimum score. Anterior nasal (AN) swabs were collected for SARS-CoV-2 RNA testing on days 0-14 and 28. Viral rebound was defined as a >=0.5 log10 RNA copies/mL increase from the immediately preceding time point to a level >=3.0 log10 RNA copies/mL, with high-level rebound defined as an increase of >=0.5 log10 copies/mL to a level >=5.0 log10 RNA copies/mL. To mirror the timing of a 5-day nirmatrelvir/ritonavir course, a supportive analysis was conducted where participants were only classified as rebounders if their rebounds occurred on or after day 5. Result(s): Symptom rebound was identified in 26% of participants at a median [Q1, Q3] of 6 [4, 9] days after study entry and 11 [9, 14] days after initial symptom onset. Individuals with symptom rebound were more likely to be female, at high risk for progression to severe disease, have shorter time since symptom onset at study entry, and have higher symptom score and higher AN viral levels day 0. Viral rebound was detected in 32%, with high-level rebound in 13% of participants. Participants with viral rebound were older, more likely to be at low risk for progression to severe disease and had higher median AN viral level at day 0. Most symptom and viral rebound were transient with 89% of symptom rebound and 95% of viral rebound events occurring for only a single day before improving. The combination of symptom and high-level viral rebound was observed in 3% of participants. In the supportive analysis of rebound occurring >=5 days after study entry, 22% and 20% of participants met symptom and viral rebound criteria, respectively, but only 1.2% of participants met criteria for both symptom and high-level viral rebound. Conclusion(s): Symptom or viral rebound in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare.
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Background: Amubarvimab and romlusevimab are anti-SARS-CoV-2 monoclonal antibodies (mAbs) that significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. SARS-CoV-2 variants (e.g., Delta, Epsilon, Lambda) harbor mutations against romlusevimab. We evaluated viral kinetics and resistance emergence in individuals treated with mono versus dual-active mAbs. Method(s): The study population included 789 non-hospitalized participants at high risk of progression to severe COVID-19 enrolled in the ACTIV-2/ A5401 platform trial (NCT04518410) and received either placebo (n=400) or amubarvimab plus romlusevimab (n=389). Anterior nasal (AN) swabs were collected for SARS-CoV-2 RNA testing on days 0-14, and 28. Spike (S) gene nextgeneration sequencing were performed on samples collected at study entry and the last sample with viral load >=2 log10 SARS-CoV-2 RNA copies per ml. We compared viral load kinetics and resistance emergence with single versus dual-active mAbs by categorizing participants as harboring variants sensitive to amubarvimab alone (Delta, Epsilon, Lambda, Mu) versus those sensitive to both mAbs (Alpha, Beta, Gamma, Others). Result(s): Study participants receiving single and dual-active mAbs had similar demographics, baseline AN viral load, baseline symptom score and duration since symptom onset. The most common SARS-CoV-2 variant in the study population was Delta (26%) followed by Gamma (19%), Alpha (12%), and Epsilon (10%). In those with successful sequencing, 37% (N=111) were infected with a variant sensitive to amubarvimab alone and 63% (N=188) were infected with a variant sensitive to both mAbs. Compared to treatment with a singleactive mAb, treatment with dual-active mAbs led to faster viral load decline at study day 3 (p=0.0001) and day 7 (p=0.003). Treatment-emergent resistance mutations were significantly more likely to be detected after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, P=0.0008). mAb resistance was also more frequently detected in the setting of single-active mAb treatment compared to dual-active mAb treatment (7.2% vs 1.1%, p=0.007). Participants with emerging mAb resistance had significantly higher pretreatment SARS-CoV-2 nasal viral RNA levels. Conclusion(s): Compared to single-active mAb therapy, dual-active mAb therapy led to significantly faster viral load decline and lower risk of emerging mAb resistance. Combination mAb therapy should be prioritized for the next generation of mAb therapeutics.
ABSTRACT
Background: The disparity in COVID-19 disease burden between European, Asian, and African countries is notable, with considerably higher morbidity and mortality in many European countries as well as the U.S. Dietary differences between regions could play a role in differential COVID-19 pathogenesis, as Western diets high in fat and sugar have been implicated in enhancing gut damage and pathogenesis during viral infections. Here we investigate the effect of diet on gut immunity and SARS-CoV-2 infection. Method(s): Six pigtail macaques were fed a commercial monkey chow diet, then transitioned to a high fat and sugar chow diet (HFD) for approximately two months prior to infection with Delta strain SARS-CoV-2. Animals were sampled prior to HFD initiation, during HFD administration but prior to infection, and for approximately one month post-infection. HFD was maintained following infection and animals were euthanized at the study conclusion. Result(s): Viral RNA was detected for up to 28 days post-infection in nose swabs, with peak viral load at day 2 at a mean of 8.2x109 copies/mL of swab fluid. Subgenomic RNA (sgRNA, indicating viral replication) decayed more rapidly, with all animals having undetectable sgRNA by day 21, and a lower peak of 2.6x109 copies/mL swab fluid on day 2. Viral RNA load was approximately 3.5 logs greater and sgRNA load approximately 3 logs higher at day 2 than in rhesus macaques infected with WA2020 SARS-CoV-2 and fed standard monkey chow. Mucosal rectal biopsies indicated significantly lower B cell frequencies from baseline to approximately two months following HFD administration (p=0.04, Dunn's), and frequencies had not recovered approximately one month postinfection. GI tract-resident IgG+ B cells were nearly absent at necropsy, with mean frequency 0.03% of total B cells. B cell loss was coupled with modest T cell expansion during HFD administration, though frequencies declined following infection. Furthermore, NK cell frequencies tended to decline from baseline throughout HFD administration, and were further depleted at necropsy one month post-infection. Conclusion(s): SARS-CoV-2 infection can induce lymphopenia, and our sampling of gut mucosal tissue indicates B cell depletion and NK cell loss with a HFD that is further exacerbated by SARS-CoV-2 infection. Excess dietary fat and sugar may disrupt gut barrier integrity and immunity, in turn predisposing the tissue to pathology of viral infection.
ABSTRACT
Background: Metformin has in vitro activity against SARS-CoV-2. In a published phase 3, quadruple-blinded, placebo-controlled randomized trial of outpatient COVID-19 therapy, metformin resulted in a 42% reduction in ER visits/hospitalizations/deaths by day 14, 58% reduction in hospitalizations/ death by day 28, and 42% reduction in Long Covid through 10 months. This analysis presents the results of viral load sampling performed during that clinical trial. Method(s): Covid-Out trial (NCT04510194) enrolled adults aged 30 to 85 within 3 days of a documented SARS-CoV-2 infection and < 7 days after symptom onset. The trial randomized 1323 participants to metformin (1000mg/day days 2-5;1500mg/day days 6 to 14), ivermectin, fluvoxamine, and/or exact-matching placebo in a 2x3 factorial trial design. Nasal swabs for viral load were an optional component, self-collected from the anterior nares on day 1, 5, and 10. Viral loads were measured via RT-qPCR using N1 and N2 targets in the SARSCoV- 2 nucleocapsid protein, with relative Ct values converted to absolute copy number via calibration to droplet digital PCR. A linear Tobit regression model was used to assess change over time while accounting for left censoring due to the viral load limit of detection. Results were adjusted for other treatment allocations within the factorial design, vaccination status, and baseline viral load. Repeated measures were accounted for using clustered standard errors within participants. Result(s): Samples were available from n = 945, 871, and 775 participants on days 1, 5, and 10, respectively. The mean change from baseline to followup was -0.64 log10 copies/mL (95%CI, -1.16 to -0.13) for metformin versus placebo, which equates to a 4.4-fold greater decrease. The mean change in SARS-CoV-2 from baseline to day 5 was -0.48 log10 copies/mL, and was -0.81 log10 copies/mL from baseline to day 10. The anti-viral effect increased with increased metformin dosing days 6-14. The antiviral effect was larger in those unvaccinated (mean -0.95 log copies/mL) than vaccinated (mean -0.39 log copies/mL). There was no change in viral load vs. placebo for ivermectin or fluvoxamine. Conclusion(s): Metformin lowered SARS-CoV-2 viral load in this quadrupleblinded, randomized clinical trial. The temporal relationship to dose titration suggests a dose-dependent effect. The magnitude of antiviral effect was similar to nirmatrelvir at day 5, greater than nirmatrelvir at day 10. Metformin is safe, widely available, and has few contraindications.
ABSTRACT
COVID-19, or SARS-CoV-2, is an extremely deadly virus that is responsible for over half a million deaths of people in the world. This virus originated in China in December 2019 and rapidly spread worldwide in 2-3 months, and affected every part of the world. Its life-threatening nature forced governments in all countries to take emergency steps of lockdown that affected the entire world's education, health, social and economic aspects. Due to the implementation of these emergencies, the population is facing psychological, social and financial problems. Additionally, this pandemic has significantly influenced the health care systems as all the resources from governments of all countries were directed to invest funds to discover new diagnostic tests and manage COVID-19 infection. The impact of the COVID-19 pandemic on the education and social life of the population is described in this article. Additionally, the diagnosis, management, and phytoremedia-tion to control the spread of COVID-19 and traditional medicinal plants' role in managing its mild symptoms have been discussed.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
Case report Dust is a known mixture and carrier of multiple allergens and an epidemiologic study demonstrated the presence of peanut proteins in school cafeterias and classrooms, suggesting that schools may play an important role in exposure to environmental food allergens. While inhalation of food allergens is a known trigger of IgE-mediate acute respiratory reaction as rhinitis and wheezing, little is known about persistent allergic asthma and/or rhinitis induced by chronic inhalation of food allergens. Here we report two cases of teenagers with nuts allergy presenting with persistent respiratory symptoms when exposed to closed and dusty environments. The first case concerns a 12-year-old boy allergic to walnut and hazelnut (specific IgE > 100 and 81.70 kU/l, respectively). For some years he has had a persistent mild asthma, frequent nasal occlusion and rhinorrhea, without any allergic sensitization to aeroallergens. Symptoms occurred exclusively during school period when he required maintenance therapy with inhaled and nasal steroids. He was asymptomatic and did not need any treatment during summer. During the lockdown period due to Covid-19 pandemic, he did not attend school for several months and he was able to discontinue inhaled corticosteroid therapy without recurrence of asthma and rhinitis symptoms. Asthma recurred after he returned to school, but with only mild intermittent symptoms, probably thanks to the use of masks and the frequent airing of the classrooms. On a single occasion he experienced nasal occlusion and rhinorrhea after that a parent had eaten hazelnut cream in the same room where he was. The second case deals with a 17-year-old boy with a history of several food allergies (milk, egg, wheat, banana, nuts, hazelnuts) and mild persistent asthma in absence of sensitization to aeroallergens. He successfully underwent oral desensitization for milk, egg and wheat in previous years. Asthma symptoms improved over the years together with progressive development of oral tolerance to food allergens for which oral immunotherapy had been done. On the other hand, he referred persistence of allergic rhinitis especially during the school year and his symptoms got worse in classroom. Exhaled nitric oxide was quite increased with evidence of eosinophils in nasal smears. In-vitro and in-vivo tests only detected food allergens sensitizations, in particolar to walnuts and hazelnuts (specific IgE were 61.00 and 55.50 kU/l respectively). These two clinical cases suggest that food allergens might be causative agents of allergic persistent asthma and/or rhinitis as aeroallergens do.