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2.
Gastroenterology ; 162(7):S-1008, 2022.
Article in English | EMBASE | ID: covidwho-1967396

ABSTRACT

BACKGROUND: Immune-modulating medications for inflammatory bowel diseases (IBD) have been associated with suboptimal vaccine responses. There is conflicting data with SARS-CoV-2 vaccination. METHODS: We measured SARS-CoV-2 vaccine immunogenicity at 2 weeks post 2nd mRNA vaccine in IBD patients as compared to normal healthy donors (NHD). We measured humoral immune responses to SARS-CoV-2: anti-spike Immunoglobulin G (IgG) and anti-receptor binding domain (RBD) IgG were measured by ELISA, and neutralizing antibody titers were measured using recombinant, reporter SARS-CoV-2. Antigen specific memory B cells were measured using recombinant SARS-CoV-2 proteins. Activation induced marker T cell (AIM) assays were performed using SARS-CoV-2 spike megapools. Immunophenotyping was performed by flow cytometry. RESULTS: We enrolled 29 patients with IBD (19 with Crohn's disease, 10 with ulcerative colitis) on infliximab (IFX) monotherapy (N=9), IFX combination therapy with a thiopurine (N=9), vedolizumab monotherapy (N= 11) as compared to matched NHD (N=12). At 2 weeks post vaccination, all subjects made detectable anti-spike IgG and anti-RBD IgG. There were no differences in anti-spike IgG titers among the different groups. IBD patients on IFX monotherapy, but not IBD patients on IFX combination therapy or vedolizumab monotherapy, had lower anti-RBD and neutralization titers as compared to NHD (p-value: 0.041 and 0.023, respectively) (Fig. 1). There were no significant differences in the percentage of spike-specific or RBD-specific memory B cells in IBD patients as compared to NHD (Fig. 1). There were no differences in the percentage of spike-specific CD4+ or CD8+ T cells in all IBD patients as compared to NHDs (Fig. 2). CONCLUSIONS: We demonstrate overall comparable and perserved cell-mediated immunity to SARS-CoV-2 vaccination in a small cohort of IBD patients treated with a range of different immune-modulating medications as compared to healthy controls. Larger numbers of patients are needed to validate these findings.

3.
2022 zh Conference on Human Factors in Computing Systems, zh EA 2022 ; 2022.
Article in English | Scopus | ID: covidwho-1846560

ABSTRACT

The digitization of financial transactions in both Global North and Global South has led to considerable shifts in how money is used, understood, and processed by users, banks, and fintechs. This shift from physical cash to digital media, accelerated by the COVID-19 push for digital transactions, has impacted how users perceive and use digital money and opened avenues for more data collection. This diverse panel proposes a discussion to understand the set of opportunities and challenges around the design of digital financial services (DFS) and data-driven decision-making in DFS. We will create a live working document starting before the panel to document the discussion, which develops during and after the panel. This live document will enable community to engage with a broader audience of researchers and industry, outlining processes, methods, and tools that researchers and practitioners have created to work with users to develop new equitable DFS and further exploration. © 2022 Owner/Author.

4.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333607

ABSTRACT

OBJECTIVE: To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19. DESIGN: A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19. SETTING: University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT). PARTICIPANTS: 956 health care workers were recruited by open invitation via UHBFT trust email and social media. INTERVENTION: Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables. RESULTS: Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity. CONCLUSIONS AND RELEVANCE: Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease. The combination of cough, and/or fever and/or anosmia identifies the majority of individuals who should self-isolate for COVID-19.

5.
Ethics & Behavior ; : 1-14, 2022.
Article in English | Taylor & Francis | ID: covidwho-1791092
6.
BJS Open ; 5(SUPPL 1):i6, 2021.
Article in English | EMBASE | ID: covidwho-1493696

ABSTRACT

Background: During the Covid-19 pandemic, non-operative management for acute appendicitis (AA) was implemented in the UK. Aim of this study was to determine the efficacy and outcomes of conservative versus surgical management of AA during the pandemic. Materials & Methods: We conducted an observational study in a tertiary referral centre. Data was collected from patients (≥16 years) with a diagnosis of AA between 1st November 2019 to 10th March 2020 (pre-COVID period) and 10th March 2020 to 5th July 2020 (COVID period). Results: A total of 116 patients in the pre-COVID period were included versus 91 in the COVID period. 43.1% (n=50) of patients pre-COVID were classified as ASA 2 compared to 26.4% (n=24) during the COVID period (p-value =0.042). 72.5% (n=66) of the patients during the COVID period scored as high risk using the Alvarado score compared to 24.1% (n=28) in the pre-COVID period (p-value<0.001).We observed a significant increase in radiological evaluation, 69.8% versus 87.5% of patients had a CT in the pre-COVID and COVID periods respectively (p-value=0.008). 94.9% of patients were managed operatively in the pre-COVID period compared to 60.4% in the COVID period (p-value<0.001). We observed more open appendicectomies (37.3% versus 0.9%;p-value<0.001) during the COVID period compared to the pre-COVID period. More abscess formation and free fluid were found intraoperatively in the COVID period (p-value= 0.021 and 0.023 respectively). Re-attendance rate due to appendicitis-related issues was significantly higher in the COVID period (p=0.027). Conclusion: Radiological diagnosis of AA was more frequent during the COVID period. More conservative management for AA was employed during the COVID-19 pandemic, and for those managed operatively an open approach was preferred. Intra-operative findings were suggestive of delayed presentation during the COVID period without this affecting the length of hospital stay.

7.
United European Gastroenterology Journal ; 9(SUPPL 8):784-785, 2021.
Article in English | EMBASE | ID: covidwho-1490980

ABSTRACT

Introduction: The Covid-19 pandemic has led to unprecedented endoscopy practice. At the peak of the pandemic in Ireland, many routine and surveillance endoscopies were deferred, with only urgent procedures prioritised. To allow safe and effective upper gastrointestinal investigations continue, alternative modalities were explored. HSE national guidance document for safe endoscopy in pandemic conditions recommends that alternative non-invasive investigation be considered for all non-urgent referrals for endoscopy. The PillCam ESO® (Given Imaging Ltd., Yoqneam, Israel) offers such an alternative for evaluation of the UGI tract. We conducted a prospective analysis of PillCam ESO® as an alternative diagnostic tool during the Covid-19 pandemic to help tackle the increasing waiting list for gastroscopy at our unit. Aims & Methods: The Aim was to assess if the PillCam ESO can identify important anatomical landmarks as stated in the British Society of Gastroenterology quality standards for upper gastrointestinal endoscopy and if it can effectively identify pathology in the Upper GI Tract. Methods: Patients who fitted our inclusion criteria were prospectively invited to participate into our trial. The three main indications were: 1. Patients with dyspepsia less than 40 years of age with no red flag symptoms, 2. Known cirrhosis to screen for varices, 3. UGI bleeds with a low Blatchford score (≤2). A local protocol for ingestion and series of positional guidelines was developed for the procedure. Ethical approval was granted for this study. Capsule transit time, endoscopic landmarks, and pathology detection were evaluated by two independent endoscopists. Results: 66 exams have been successfully performed in the GI Lab from June 2020 to date without complications. The two frequent indications were dyspepsia (66%) and abdominal pain (24%). IM Metoclopramide was administered in 52% of cases. Complete visualisation of the following major anatomical landmarks was achieved in 100% of cases: Oesophagus, Oesophageal-gastro junction, and Gastric. A full view of the cardia, fundus, greater curve, lesser curve, incisura angularis, antrum, pylorus, and second part of Duodenum was obtained in 99%, 94%, 99%, 97%, 97%, 92%, 91%, and 80% of cases, respectively. D2 intubation was achieved in 80% of cases. The mean capsule transit times was 62 mins (SD 28). A normal exam was reported in 41% of cases. Reflux oesophagitis and gastritis were the most common pathology detected. Adenocarcinoma of the OG junction was detected in 1 case. Conclusion: The PillCam ESO achieves excellent views of the upper GI tract. In selective cases, it is a safe alternative to gastroscopy which may help reduce gastroscopy waiting times.

8.
Journal of the American College of Surgeons ; 233(5):e62-e63, 2021.
Article in English | EMBASE | ID: covidwho-1466563

ABSTRACT

Introduction: Management of upper gastrointestinal (UGI) leaks is challenging, especially in patients with delayed presentation and established sepsis. Endoluminal vacuum therapy (EVT) is an emerging treatment strategy which may reduce morbidity and mortality compared to traditional treatments in this patient group. We report the outcomes for patients with UGI leaks treated with EVT in a tertiary UK hospital over a 10-year period. Methods: Between April 2011 and February 2021, 63 patients with UGI leaks from different causes were treated with EVT using an ad-hoc endoluminal vacuum device (EVD). Information related to treatment and outcome was recorded prospectively. Results: Patients had a median age of 67 years (25-92), and mean Apache II score of 20.7 (6-36) at the time of leak diagnosis. The cause of the leak was anastomotic (n=23;37%), iatrogenic (n=20;32%), spontaneous (n=19;30%), and traumatic (n=1;2%). Forty-seven (75%) leaks were oesophageal, 12 (19%) gastric, 2 (3%) duodenal, and 1 (2%) pharyngeal. The median number of EVD changes required to heal the leak was 9 (1-27), and median length of hospital stay was 31 days (1-196). Successful resolution of the leak occurred in 55 (87%) patients. Eight (13%) patients died during treatment. There were no complications related to insertion of the EVD. Eight (13%) patients had complications during treatment which required further intervention including bleeding (n=4;6%), stroke (n=1;2%), pulmonary embolus (n=1;2%), myocardial infarction (n=1;2%) and COVID-19 (n=1;2%). Conclusion: EVT is safe, and can be used to successfully treat UGI leaks from a disparate range of leak causes in critically unwell patients. Further studies are required to develop a standardized procedure to enable broader adoption of EVT in this group of patients.

9.
Clin Pharmacol Ther ; 108(4): 775-790, 2020 10.
Article in English | MEDLINE | ID: covidwho-1384148

ABSTRACT

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90 ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax ) at an approved dose in humans (Cmax /EC90 ratio). Only 14 of the 56 analyzed drugs achieved a Cmax /EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax /half-maximal effective concentration (EC50 ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Delivery Systems/methods , Drug Repositioning/methods , Pneumonia, Viral/drug therapy , Antiviral Agents/blood , COVID-19 , Coronavirus Infections/blood , Humans , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2
10.
Adv Drug Deliv Rev ; 178: 113848, 2021 11.
Article in English | MEDLINE | ID: covidwho-1283843

ABSTRACT

The emergence of SARS-CoV-2, and the ensuing global pandemic, has resulted in an unprecedented response to identify therapies that can limit uncontrolled inflammation observed in patients with moderate to severe COVID-19. The immune pathology behind COVID-19 is complex and involves the activation and interaction of multiple systems including, but not limited to, complement, inflammasomes, endothelial as well as innate and adaptive immune cells to bring about a convoluted profile of inflammation, coagulation and tissue damage. To date, therapeutic approaches have focussed on inhibition of coagulation, untargeted immune suppression and/or cytokine-directed blocking agents. Regardless of recently achieved improvements in individual patient outcomes and survival rates, improved and focussed approaches targeting individual systems involved is needed to further improve prognosis and wellbeing. This review summarizes the current understanding of molecular and cellular systems involved in the pathophysiology of COVID-19, and their contribution to pathogen clearance and damage to then discuss possible therapeutic options involving immunomodulatory drug delivery systems as well as summarising the complex interplay between them.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Delivery Systems/methods , Immunologic Factors/administration & dosage , Inflammasomes/antagonists & inhibitors , Adjuvants, Immunologic/administration & dosage , Animals , Antiviral Agents/immunology , COVID-19/immunology , Communicable Diseases/drug therapy , Communicable Diseases/immunology , Complement Activation/drug effects , Complement Activation/immunology , Drug Delivery Systems/trends , Humans , Immunologic Factors/immunology , Inflammasomes/immunology
11.
Endoscopy ; 53(SUPPL 1):S128-S129, 2021.
Article in English | EMBASE | ID: covidwho-1254050

ABSTRACT

Aims At the peak of the Covid-19 pandemic in Ireland, many routine and surveillance endoscopies were deferred, with onlyurgent procedures prioritised. The PillCam ESO (Given Imaging Ltd., Yoqneam, Israel) is a non-invasive investigation, whichoffers an alternative method of evaluating the UGI tract for non-urgent referrals for endoscopy. A prospective study to assess if the PillCam ESO can identify important anatomical landmarks stated in the British Societyof Gastroenterology quality standards for upper gastrointestinal endoscopy and pathology in the Upper GI Tract. Methods Patients who fitted our inclusion criteria were prospectively invited to participate into our trial. The three main indications were 1;patients with dyspepsia less than 40 years of age with no red flag symptoms, 2;knowncirrhosis to screen for varices, 3;UGI bleeds with a low Blatchford score (≤2). A local protocol for ingestion and series of positional guidelines was developed for the procedure. Endoscopic landmarks, and pathology detection were evaluated by two independent endoscopists. Results 32 exams have been successfully performed from June 2020 to date without complications. The two frequentindications were dyspepsia (66 %) and abdominal pain (19 %). Metoclopramide was administered in 66 % of cases. Visualisation of the following major anatomical landmarks was achieved in 100 % of cases: Oesophagus, oesophageal-gastro junction, greater curve, pylorus. A full view of the cardia, fundus, lesser curve, incisura angularis and antrum was obtained in 97 %, 87 %, 93 %, 97 % and97 % of cases, respectively. D2 intubation was achieved in 90 % of cases. A normal exam was reported in 34 % of cases.Reflux oesophagitis and gastritis were the most common pathology detected. Adenocarcinoma of the OG junction wasdetected in 1 case. Conclusions The PillCam ESO achieves excellent views of the upper GI tract. In selective cases, it is a safe alternative togastroscopy which may help reduce gastroscopy waiting times.

12.
Nanoscale ; 13(13): 6410-6416, 2021 Apr 07.
Article in English | MEDLINE | ID: covidwho-1189295

ABSTRACT

The control of COVID-19 across the world requires the formation of a range of interventions including vaccines to elicit an immune response and immunomodulatory or antiviral therapeutics. Here, we demonstrate the nanoparticle formulation of a highly insoluble drug compound, niclosamide, with known anti SARS-CoV-2 activity as a cheap and scalable long-acting injectable antiviral candidate.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Niclosamide , SARS-CoV-2/drug effects , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Humans , Injections, Intramuscular , Nanoparticles , Niclosamide/administration & dosage , Niclosamide/pharmacology
13.
Br J Clin Pharmacol ; 87(4): 2078-2088, 2021 04.
Article in English | MEDLINE | ID: covidwho-883246

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic and urgent treatment and prevention strategies are needed. Nitazoxanide, an anthelmintic drug, has been shown to exhibit in vitro activity against SARS-CoV-2. The present study used physiologically based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported SARS-CoV-2 EC90 . METHODS: A whole-body PBPK model was validated against available pharmacokinetic data for healthy individuals receiving single and multiple doses between 500 and 4000 mg with and without food. The validated model was used to predict doses expected to maintain tizoxanide plasma and lung concentrations above the EC90 in >90% of the simulated population. PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. RESULTS: The PBPK model was successfully validated against the reported human pharmacokinetics. The model predicted optimal doses of 1200 mg QID, 1600 mg TID and 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12 hours post dose was estimated. CONCLUSION: The PBPK model predicted tizoxanide concentrations within doses of nitazoxanide already given to humans previously. The reported dosing strategies provide a rational basis for design of clinical trials with nitazoxanide for the treatment or prevention of SARS-CoV-2 infection. A concordant higher dose of nitazoxanide is now planned for investigation in the seamless phase I/IIa AGILE trial.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , COVID-19/prevention & control , Drug Repositioning , Models, Biological , Nitro Compounds/administration & dosage , Thiazoles/administration & dosage , Adult , Antiviral Agents/blood , Antiviral Agents/pharmacokinetics , COVID-19/blood , Computer Simulation , Drug Dosage Calculations , Female , Humans , Lung/metabolism , Male , Middle Aged , Nitro Compounds/blood , Nitro Compounds/pharmacokinetics , Reproducibility of Results , Thiazoles/blood , Thiazoles/pharmacokinetics , Tissue Distribution , Young Adult
14.
Preprint in English | medRxiv | ID: ppmedrxiv-20087130

ABSTRACT

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibit in vitro activity against SARS-CoV-2. Nitazoxanide is an anthelmintic drug and its metabolite tizoxanide has been described to have broad antiviral activity against influenza and other coronaviruses. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide 90% effective concentration (EC90) against SARS-CoV-2. MethodsA whole-body PBPK model was constructed for oral administration of nitazoxanide and validated against available tizoxanide pharmacokinetic data for healthy individuals receiving single doses between 500 mg - 4000 mg with and without food. Additional validation against multiple-dose pharmacokinetic data when given with food was conducted. The validated model was then used to predict alternative doses expected to maintain tizoxanide plasma and lung concentrations over the reported nitazoxanide EC90 in >90% of the simulated population. Optimal design software PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. ResultsThe PBPK model was validated with AAFE values between 1.01 - 1.58 and a difference less than 2-fold between observed and simulated values for all the reported clinical doses. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food, to provide tizoxanide plasma and lung concentrations over the reported in vitro EC90 of nitazoxanide against SARS-CoV-2. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. ConclusionThe PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC90 for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection.

15.
Preprint in English | medRxiv | ID: ppmedrxiv-20068379

ABSTRACT

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, this has not been accompanied by a comprehensive evaluation of the ability of these drugs to achieve target plasma and lung concentrations following approved dosing in humans. Moreover, most publications have focussed on 50% maximum effective concentrations (EC50), which may be an insufficiently robust indicator of antiviral activity because of marked differences in the slope of the concentration-response curve between drugs. Accordingly, in vitro anti-SARS-CoV-2 activity data was digitised from all available publications up to 13th April 2020 and used to recalculate an EC90 value for each drug. EC90 values were then expressed as a ratio to the achievable maximum plasma concentrations (Cmax) reported for each drug after administration of the approved dose to humans (Cmax/EC90 ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC90 ratio above 1 meaning that plasma Cmax concentrations exceeded those necessary to inhibit 90% of SARS-CoV-2 replication. A more in-depth assessment of the putative agents tested demonstrated that only nitazoxanide, nelfinavir, tipranavir (boosted with ritonavir) and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval at their approved human dose. For all drugs reported, the unbound lung to plasma tissue partition coefficient (KpUlung) was also simulated and used along with reported Cmax and fraction unbound in plasma to derive a lung Cmax/EC50 as a better indicator of potential human efficacy (lung Cmax/EC90 ratio was also calculable for a limited number of drugs). Using this parameter hydroxychloroquine, chloroquine, mefloquine, atazanavir (boosted with ritonavir), tipranavir (boosted with ritonavir), ivermectin, azithromycin and lopinavir (boosted with ritonavir) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50. This analysis was not possible for nelfinavir because insufficient data were available to calculate KpUlung but nitozoxanide and sulfadoxine were also predicted to exceed their reported EC50 by 3.1- and 1.5-fold in lung, respectively. The antiviral activity data reported to date have been acquired under different laboratory conditions across multiple groups, applying variable levels of stringency. However, this analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds which are unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.

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