SARS-CoV-2 omicron variants succumb in vitro to Artemisia annua hot water extracts (preprint)

The SARS-CoV-2 (COVID-19) global pandemic continuous to infect and kill millions while rapidly evolving new variants that are more transmissible and evading vaccine-elicited antibodies. Artemisia annua L. extracts have shown potency against all previously tested variants. Here we further queried extract efficacy against omicron and its recent subvariants. Using Vero E6 cells, we measured the in vitro efficacy (IC50) of stored (frozen) dried-leaf hot-water A. annua L. extracts of four cultivars (A3, BUR, MED, and SAM) against SARS-CoV-2 variants: original WA1 (WT), BA.1.1.529+R346K (omicron), BA.2, BA.2.12.1, and BA.4. IC50 values normalized to the extract artemisinin (ART) content ranged from 0.5-16.5 uM ART. When normalized to dry mass of the extracted A. annua leaves, values ranged from 20-106 ug. Although IC50 values for these new variants are slightly higher than those reported for previously tested variants, they were within limits of assay variation. There was no measurable loss of cell viability at leaf dry weights less than or equal to 50 ug of any cultivar extract. Results continue to indicate that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective approach to help stave off this pandemic virus and its rapidly evolving variants.

The Indirect Victims of COVID-19: Perception of Non-COVID-19 Patients about the Effect of Closure of the Medical Outpatient Services on their Health.

BACKGROUND: In order to reduce COVID-19 transmission and protect healthcare workers, the outpatient departments (OPDs) in many hospitals worldwide were closed down in the early days of the pandemic. Patients being managed for chronic medical illnesses who subsequently suffered reduced access to healthcare have been described as "the patients left behind". AIM: The study aimed at assessing the impact of the closure of the Medical OPD in University of Ilorin Teaching Hospital (UITH) on the health and perceived well-being of patients with chronic medical illnesses. METHODS: A cross-sectional study of 180 patients with chronic medical illnesses attending the MOPD in UITH. RESULTS: Mean age of participants was 50.2±18.2years, 92 (51.1%) were male, median duration of attending MOPD was 21 months (IQR 12-36). 92 patients (51.1%) perceived a negative affectation of their well-being by the closure of MOPD. Being >50 years was associated with a perception of negative affectation of well-being (P=0.042). 140 patients (77.8%) had clinic appointments that fell within the period under review. 67(69.3%) of the 97 patients who had medical complaints during the period could not reach a doctor and this was associated with a perception of negative affectation of their wellbeing. The commonest action they took was to do nothing (28.3%), three (4.5%) resorted to herbal concoctions. 19 (29.9%) felt their complaints were urgent. CONCLUSION: Our study identifies that patients with chronic medical illness are potential victims of COVID-19 related disruption of healthcare services. Healthcare managers in Nigeria must develop alternatives such as telemedicine that sustain face-to-face medical interaction during eventualities.

CONTEXTE: Afin de réduire la transmission de la COVID-19 et protéger les travailleurs de la santé, les services ambulatoires (OPD) dans de nombreux hôpitaux dans le monde ont été fermés dans les premiers jours de l'Pandémie. Patients pris en charge pour des maladies chroniques quipar la suite souffert d'un accès réduit aux soins de santé ont été décrit comme "les patients laissés pour compte". OBJECTIF: L'étude visait à évaluer l'impact de la fermeture de l'OPD médical à l'hôpital universitaire d'Ilorin (UITH) la santé et le bien-être perçu des patients atteints de chroniquesMaladies. MÉTHODES: Une étude transversale de 180 patients atteints de chroniques maladies médicales fréquentant le MOPD à l'UITH. RÉSULTATS: L'âge moyen des participants était de 50.2 ±18.2 ans, 92 ans(51.1 %) étaient des hommes, la durée médiane de la participation au MOPD était de 21mois (IQR 12-36). 92 patients (51.1 %) ont perçu un résultat negative l'affectation de leur bien-être par la fermeture du MOPD. Être >50ans était associée à une perception d'affectation négative de bien-être (P= 0.042). 140 patients (77.8 %) avaient des rendez-vous à la clinique qui s'inscrivait dans la période considérée. 67 (69.3 %) des 97 patients qui ont eu des problèmes médicaux au cours de la période n'ont pas pu atteindre un et cela était associé à une perception d'affectation negative de leur bien-être. L'action la plus courante qu'ils ont prise était de ne rien faire (28.3%), deux (4.5%) ont eu recours à des concoctions à base de plantes. 19 (29.9 %) ont ressenti leurs plaintes étaient urgentes. CONCLUSION: Notre étude identifie que les patients atteints demaladie chronique les maladies médicales sont des victimes potentielles des perturbations liées à la COVID-19des services de santé. Les gestionnaires de soins de santé au Nigeria doivent se developper des solutions de rechange comme la télémédecine qui soutiennent la médecine en personne interaction lors d'éventualités. Mots-clés: Maladie COVID-19, Maladies chroniques, COVID-19 fermeture connexe des services médicaux ambulatoires, perception.

TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features.

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.

Artemisia annua hot-water extracts show potent activity in vitro against Covid-19 variants including delta (preprint)

Ethnopharmacological relevanceFor millennia in Southeast Asia, Artemisia annua L. was used to treat "fever". This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria. Aim of the StudyThe SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. Materials and MethodsUsing Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five fully infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1). ResultsIn addition to being effective against the original wild type WA1, A. annua cultivars A3, BUR, MED and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3-8.4 M and 1.4-25.0 M, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0-67.7 g DW and 59.5-160.6 g DW, respectively. Cell toxicity was insignificant at a leaf dry weight of [≤]50 g in the extract of any cultivar. ConclusionsResults suggest that oral consumption of A. annua hot-water extracts (tea infusions), could provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.

A Randomized Single Blind Controlled Trial of Combination Therapy (Spironolactone and Sitagliptin) in Hospitalized Adult Patients with Covid-19 (preprint)

Background: COVID-19 may cause respiratory distress syndrome, ICU admission and death. Treatment of COVID-19 to prevent hospitalization, respiratory distress syndrome and death remains a priority. Our investigation sought to determine whether combination of spironolactone and Sitagliptin could reduce hospitalization for outpatient and death for inpatient with SARS-CoV-2 infection.Methods: This single blind, 4-arms, prospective randomized clinical trial was conducted at Shiraz University of Medical Sciences and Bushehr University of Medical Sciences hospitals during the second wave of the COVID-19 pandemic between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into four groups: control (standard therapy), combination (Sitagliptin, spironolactone and standard therapy), Sitagliptin (Sitagliptin and standard therapy) or spironolactone (spironolactone and standard therapy). The primary outcome was the clinical improvement of the patients in the hospital as measured on an eight-point numerical scale ranging from no limitation of activities (score 1) to death (score 8). The secondary outcomes included intubation, ICU admission, end organ damages, CT findings and paraclinical information. We also treated 60 outpatients with SARS-CoV-2 infection to assess hospitalization rate.Results: 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), Sitagliptin group (66 patients) and Spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes. However, the mortality rate was lower in spironolactone receivers. Our intervention reduced lung infiltration but not the area of involvement in lung. The combination (Sitagliptin, spironolactone) therapy for outpatients with SARS-CoV-2 infection could reduce hospitalization rate to less than 2 percent.Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients. Furthermore, early prescription of this combination can reduce hospitalization rate.Clinical Trial Registration Details: IRCT registration number: IRCT20201003048904N2, Registration date: December 10, 2020. Funding Information: This project is supported by Shiraz University of Medical Sciences, Bushehr University Medical Sciences, Faghihi Hospital and Shohadaye_Khalije_Fars Hospital. Declaration of Interests: The author has declared that no conflict of interest exists.Ethics Approval Statement: The ethics committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1399.550) and Bushehr University of Medical Sciences (IR.BPUMS.REC.1399.140) approved the study. We followed the declaration of Helsinki and Iranian national guidelines for ethics in research to design the study. The research physicians had routinely collected a written formal informed consent at the time of admission.

The COVID-19 Pandemic, Socioeconomic Effects, and Intimate Partner Violence Against Women: A Population-Based Cohort Study in Iran (preprint)

Background: Intimate partner violence (IPV) is a significant public health challenge. IPV hotlines in high-income settings have reported rising numbers of calls in the COVID-19 pandemic era. However, no systematic studies to examine prevalence and risk factors of IPV have transpired. We investigated the prevalence, pattern, and socioeconomic risk factors of IPV pre- and six months after the onset of pandemic (hereafter post-pandemic) among a cohort of Iranian women.Methods: Our population-based IPV survey was conducted before the onset of the COVID-19 epidemic in Iran, when we interviewed 2502 partnered Iranian women aged 18-60 years. We conducted a follow-up measurement six months later (n=2116). Prevalence and first-time incidence (FTI) of psychological, physical, and sexual IPV and their 95% confidence interval (CI) were estimated. Adjusted Odds Ratio (OR) and their 95% CI were estimated.Results: The post-pandemic prevalence of IPV (65∙4%; CI: 63∙4%- 67∙4%) was higher than pre-pandemic prevalence (54∙2%; CI: 52∙2%- 56∙3%). At follow up, FTI of IPV was 25∙5% (CI: 22∙9%- 28∙4%). The highest increase of FTI was observed in cases of physical and sexual IPV. Being employed was correlated with IPV (OR: 0∙42; CI: 0∙25- 0∙68). Having the highest socioeconomic status (OR: 0∙04; CI: 0∙01- 0∙17) and a full-time employed partner (OR: 0∙02; CI: 0∙01- 0∙03) were correlated with physical IPV.Interpretation: The prevalence and severity of IPV have increased following the onset of the COVID-19 pandemic. Unemployment of women or their partners and pre-pandemic lower socioeconomic status are risk factors of IPV against women without previous experience of IPV. Monitoring programs should target these populations to prevent IPV. Guidelines for addressing IPV in the context of the COVID-19 pandemic need to be adapted for low- and middle-income countries.Funding: Vice-Chancellor for Research, Shiraz University of Medical SciencesDeclaration of Interests: The authors declare that there is no conflict of interests.Ethics Approval Statement: The study protocol was approved by the Institutional Review Board (IRB) of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1399.301).

Clinical Decision Tools to Predict Orotracheal Intubation and In-Hospital Mortality Among COVID-19 Patients: A Retrospective Multi-Centre Study (preprint)

Background: COVID-19 is declared a global pandemic by the World Health Organization in March 2020 and since then has been significantly challenging health care services. Validated clinical rules are urgently needed to assist clinicians in their decision-making process in identifying admitted COVID-19 patients at risk of in-hospital mortality and mechanical ventilation and appropriately allocating limited health care resources. Methods: A multi-centre observational study was performed on admitted COVID-19 patients between 1 March and 31 May 2020 in Iran. Patient characteristics, clinical manifestations and association with in-hospital mortality and orotracheal intubation were reported. Logistic regression analyses were used to derive predictive clinical tools and the model scoring derived from the coefficients. General bootsrap procedure was used for internal validation. External validation was performed on a randomly selected admitted COVID-19 patients. Findings: 4566 admitted COVID positive patients (2074 females and 2492 males) were enrolled with a median age of 59 years. The most common presentations were dyspnoea (53%), cough (53%), and fever (52%). 64% of patients had O2 saturation below 93% at the time of presentation. Orotracheal intubation was required in 298 of patients (7%) and 628 of patients (14%) died during admission. The features associated with in-hospital mortality were: age more than 65 years, arrival by ambulance, dyspnoea, orotracheal intubation, O2 saturation below 93%, and a history of malignancy. The features associated with orotracheal intubation were: age more than 65 years, arrival by ambulance, dyspnoea, loss of consciousness, prior contact with a confirmed COVID case, and O2 saturation below 93%. External validations confirmed good discrimination with an area under the curve of 0·826 and 0·734 for in-hospital mortality and orotracheal intubation, respectively. Interpretation: Clinical decision tools to predict mortality and requirement for mechanical ventilation will assist clinicians in appropriately making decision of their patients. Funding: No fundingDeclaration of Interests: The authors declare no competing interests.Ethics Approval Statement: Ethical considerations for the study were reviewed and approval granted by the ethics committee of Isfahan University of Medical Sciences with approval number of IR.MUI.MED.REC 1399.423.