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1.
Clin Exp Rheumatol ; 39 Suppl 130(3): 108-114, 2021.
Article in English | MEDLINE | ID: covidwho-1819217

ABSTRACT

OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors. METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment. RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01). CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.


Subject(s)
COVID-19 , Fibromyalgia , Anxiety/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Depression/epidemiology , Disease Outbreaks , Fibromyalgia/diagnosis , Fibromyalgia/epidemiology , Fibromyalgia/therapy , Humans , SARS-CoV-2 , Surveys and Questionnaires
2.
Phytother Res ; 35(10): 5417-5426, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1479439

ABSTRACT

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first occurred in China in December 2019 and subsequently spread all over the world with cardiovascular, renal, and pulmonary symptoms. Therefore, recognizing and treating the cardiovascular sign and symptoms that caused by coronavirus disease 2019 (COVID-19) can be effective in reducing patient mortality. To control the COVID-19-related cardiovascular symptoms, natural products are considered one of the promising choices as complementary medicine. Scientists are struggling to discover new antiviral agents specific to this virus. In this review, the natural products for management of cardiovascular symptoms of COVID-19 are categorized into three groups: (a) natural products with an impact on angiotensin II type 1 receptor; (b) natural products that inhibit angiotensin-converting enzyme activity; and (c) natural products that mimic adenosine activity. All these natural products should undergo clinical investigations to test their efficacy, safety, and toxicity in the treatment of cardiovascular symptoms of COVID-19. This article summarizes agents with potential efficacy against COVID-19-related cardiovascular symptoms.


Subject(s)
Biological Products , COVID-19 , Angiotensin-Converting Enzyme Inhibitors , Antiviral Agents/therapeutic use , Biological Products/therapeutic use , Humans , SARS-CoV-2
3.
Pharmacol Res ; 157: 104872, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318931

ABSTRACT

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , COVID-19 , Humans , Pandemics , SARS-CoV-2
4.
Nat Prod Res ; : 1-20, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1216554

ABSTRACT

Viral diseases have always played an important role in public and individual health. Since December 2019, the world is facing a pandemic of SARS-CoV-2, a coronavirus that results in a syndrome known as COVID-19. Several studies were conducted to implement antiviral drug therapy, until the arrival of SARS-CoV-2 vaccines. Numerous scientific investigations have considered some nutraceuticals as an additional treatment of COVID-19 patients to improve their clinical picture. In this review, we would like to emphasize the studies conducted to date about this issue and try to understand whether the use of nutraceuticals as a supplementary therapy to COVID-19 may be a valid and viable avenue. Based on the results obtained so far, quercetin, astaxanthin, luteolin, glycyrrhizin, lactoferrin, hesperidin and curcumin have shown encouraging data suggesting their use to prevent and counteract the symptoms of this pandemic infection.

5.
Curr Pharm Des ; 27(9): 1185-1193, 2021.
Article in English | MEDLINE | ID: covidwho-1206238

ABSTRACT

SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, chloroquine and hydroxychloroquine, against SARS-CoV-2, have shown to be a potential area of interest for drug development due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discussed analogs of the drugs to understand the quinoline scaffold's potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways, primarily through the modification of its substituents. We studied these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle, pre and post entry. In this study, we reviewed chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of viruses. Furthermore, we reviewed the compound's potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to chloroquine can act as antivirals or attenuate symptoms through the stimulation of the host immune system or reduction of oxidative stress. Furthermore, we discuss perspectives of the drug's repurposing due to its ability to inhibit the beta-hematin formation and to be a Zinc Ionophore.


Subject(s)
COVID-19 , Chloroquine , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/pharmacology , Humans , SARS-CoV-2
6.
Curr Pharmacol Rep ; 7(3): 102-106, 2021.
Article in English | MEDLINE | ID: covidwho-1202878

ABSTRACT

COVID-19 represents the biggest health challenge. Although the mortality rate of COVID-19 is low, the high numbers of infected people and those with post-COVID-19 symptoms represent a real problem for the health system. A high number of patients with COVID-19 or people recovered from COVID-19 suffer from a dry cough and/or myalgia. Interestingly, an imbalance in bradykinin was observed in COVID-19 patients, which might be due to the accumulation of bradykinin as a result of a reduction in the degradation of bradykinin. This finding inspired the idea of possible similitude between the dry cough that is induced by angiotensin-converting enzyme inhibitors and the COVID-19-induced dry cough. Both of these types of cough are mediated, at least partially, by bradykinin. They both manifested as a persistent dry cough that is not responded to traditional dry cough remedies. However, several drugs were previously investigated for the treatment of angiotensin-converting enzyme inhibitor-induced dry cough. Here, we hypothesized that such treatment might be useful in COVID-19-induced dry cough and other bradykinin-related symptoms such as generalized pain and myalgia. In this article, evidence was presented to support the use of indomethacin as a potential treatment of COVID-19-induced dry cough. The choice of indomethacin was based on its ability to suppress the cyclooxygenase enzyme while also lowering the level of the inflammatory mediator bradykinin. Furthermore, indomethacin has been shown to be effective in treating angiotensin-converting enzyme inhibitor-induced dry cough. Moreover, indomethacin is a long-established, low-cost, effective, and readily available medication.

7.
Adv Integr Med ; 7(4): 218-221, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-896774

ABSTRACT

Oral doses of certain essential oils may reduce symptoms of acute respiratory infections of viral origin. It is likely that the commercially available essential oil capsules Myrtol® (a mixture of essential oils of eucalyptus Eucalyptus globulus, sweet orange Citrus sinensis, myrtle Myrtus communis and lemon Citrus limonum) and Tavipec® (spike lavender Lavandula latifolia) could also provide mild to moderate symptom relief in patients with viral respiratory diseases. Myrtol® may also improve the course (duration and severity) of acute bronchitis of viral origin, in humans. Both products were well tolerated, with most of the mild to moderate side-effects affecting the gastrointestinal tract. This review found no research evidence describing the clinical effect of inhalation of essential oils for acute respiratory viral infections.


Clinical evidence from published clinical trials identified in this rapid review suggests that oral administration of blends of certain essential oils (EO) can reduce symptoms of acute respiratory infections of viral origin in humans, namely acute sinusitis and acute bronchitis.There is clinical evidence for orally administered Lavandula latifolia essential oil (Tavipec®) (n = 2) and a blend of essential oils of Eucalyptus globulus, Citrus sinensis, Myrtus communis and lemon Citrus limonum (Myrtol® and its successors GeloMyrtol® and GeloMyrtol®Forte) (n = 3) to reduce symptoms of acute sinusitis and acute bronchitis of viral origin(s) [[1], [2], [3], [4], [5]]. All five clinical trials relied mostly on (subjective) symptom scores to determine the treatment effect. Differences between treatment and placebo symptom scores in these clinical trials were statistically significant, although the differences in absolute numbers were small. Furthermore, clinical evidence suggests that Myrtol® is also able to improve the course (duration and severity) of acute bronchitis of viral origin, in humans [3,5].No clinical evidence was found on whether EO can also improve symptoms and/or course of other acute respiratory infections, like influenza or acute respiratory distress syndrome caused by viruses of the coronavirus class. Further clinical trials with these and other EO (or blends of EO), and other administration forms, like steam inhalation or personal inhalers, are warranted to further elucidate the potential of commonly available EOs in treating acute respiratory infections of viral origin, especially influenza and COVID-19.

8.
Ir J Psychol Med ; 38(4): 249-257, 2021 12.
Article in English | MEDLINE | ID: covidwho-1169339

ABSTRACT

OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic and its associated restrictions on a cohort of patients with severe and enduring mental illness treated with clozapine. METHODS: Semi-structured interviews were conducted with 63 individuals attending a clozapine clinic within the Galway-Roscommon Mental Health Services to determine the impact of COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life, by utilising Likert scale data. The Beck Anxiety Inventory (BAI) and Hamilton Anxiety Rating Scale (HAM-A) were additionally utilised to measure anxiety symptoms cross-sectionally. RESULTS: Anxiety symptoms were low with a median BAI score of 4.0 and HAM-A score of 4.0. Likert scale measurements recorded only a modest adverse impact of COVID-19 restrictions on anxiety and depressive symptoms, quality of life and occupational and social functioning. Free-text comments from patients (n = 55), were grouped into five themes: neutral impact (n = 22), negative psychological impact (n = 13), negative social impact (n = 11), positive psychological impact (n = 5) and media coverage inducing anxiety (n = 4). CONCLUSIONS: Three months into the COVID-19 pandemic and its restrictions, the impact on individuals with treatment-resistant psychotic disorders attending a clozapine clinic has been modest, with preliminary evidence demonstrating minimal increases in subjective symptoms of anxiety and reduced social functioning. Reduced social engagements and supports attainable both within the community and from mental health services were noted by some participants.


Subject(s)
COVID-19 , Clozapine , Clozapine/therapeutic use , Humans , Pandemics , Quality of Life , SARS-CoV-2
9.
Clin Cosmet Investig Dent ; 13: 47-50, 2021.
Article in English | MEDLINE | ID: covidwho-1160383

ABSTRACT

AIM: This case series demonstrated that phthalocyanine derivate mouthwash is a promising alternative for reducing the viral load of SARS-CoV-2 and for clinical improvement of infected patients who presented mild and moderate symptoms. PURPOSE: The aim of this study was to report a case series of patients diagnosed with COVID-19 that used the phthalocyanine derivate mouthwash to reduce clinical symptoms. PATIENTS AND METHODS: Eight patients used 5mL of phthalocyanine derivate mouthwash gargling/rinsing for one minute, five times daily, over a fourteen day period. Two measurement scales were applied for each patient in different periods to verify sore throat - VAS - Visual Analogue Scale for Pain and the clinical conditions - PS - Performance Status. RESULTS: All patients presented a significant reduction in clinical symptoms with the use of the mouthwash for gargling/rinsing after few days of use, without hospitalization. CONCLUSION: The phthalocyanine derivate mouthwash protocol appears as a potential alternative for clinical improvement of COVID-19 infected patients. Daily use of this mouthwash rapidly reduced clinical symptoms such as sore throats, cough and mouth ulcers. Large, high-quality randomized controlled trials with larger sample size are necessary to confirm the effectiveness of this mouthwash protocol against COVID-19.

10.
11.
PLoS One ; 16(3): e0248367, 2021.
Article in English | MEDLINE | ID: covidwho-1127797

ABSTRACT

BACKGROUND: Placebos can reduce physical symptoms even when provided with full honesty and disclosure. Yet, the precise mechanisms underlying the effects of "open-label placebos" (OLPs) have remained subject of debate. Furthermore, it is unclear whether OLPs are similarly effective when provided remotely, as is sometimes required e.g. in the current COVID-19 pandemic. METHODS: In a randomized-controlled trial, we examined the effects of OLP plus treatment as usual (TAU) compared to TAU alone on symptom reduction in people with allergic rhinitis (N = 54) over the course of two weeks. Due to the COVID-19 pandemic, OLP was provided remotely (i.e. sent via postal service). To investigate the potential influence of the clinical encounter on the effects of OLP, we manipulated the perception of the virtual clinical encounter, both with respect to verbal and nonverbal factors (augmented vs. limited encounter). RESULTS: The results of the manipulation check confirmed that the augmented clinical encounter was evaluated more positively than the limited encounter, in terms of perceived warmth of the provider. Participants from all treatment groups showed significant symptom reduction from baseline to two weeks later, but OLP had no incremental effect over TAU. Participants benefitted more from OLP when they did not take any other medication against allergic symptoms than when taking medication on demand. When controlling for baseline symptoms, a significant treatment by encounter interaction was found, pointing to greater symptom improvement in the OLP group when the encounter was augmented, whereas the control group improved more when the encounter was limited. DISCUSSION: The study demonstrates that providing OLP and enhancing the encounter remotely is possible, but their effectiveness might be lower in comparison to previous studies relying on physical patient-provider interaction. The study raises questions for future research about the potential and challenges of remote placebo studies and virtual clinical encounters. The study has been registered as a clinical trial at ISRCTN (record number: 39018).


Subject(s)
Anti-Allergic Agents/therapeutic use , Rhinitis, Allergic/drug therapy , Telemedicine , Adolescent , Adult , Female , Humans , Male , Middle Aged , Physician-Patient Relations , Placebo Effect , Young Adult
12.
Lancet Psychiatry ; 8(2): 141-149, 2021 02.
Article in English | MEDLINE | ID: covidwho-1127095

ABSTRACT

BACKGROUND: There is major concern about the impact of the global COVID-19 outbreak on mental health. Several studies suggest that mental health deteriorated in many countries before and during enforced isolation (ie, lockdown), but it remains unknown how mental health has changed week by week over the course of the COVID-19 pandemic. This study aimed to explore the trajectories of anxiety and depression over the 20 weeks after lockdown was announced in England, and compare the growth trajectories by individual characteristics. METHODS: In this prospective longitudinal observational study, we analysed data from the UCL COVID-19 Social Study, a panel study weighted to population proportions, which collects information on anxiety (using the Generalised Anxiety Disorder assessment) and depressive symptoms (using the Patient Health Questionnaire) weekly in the UK since March 21, 2020. We included data from adults living in England who had at least three repeated measures between March 23 and Aug 9, 2020. Analyses were done using latent growth models, which were fitted to account for sociodemographic and health covariates. FINDINGS: Between March 23, and Aug 9, data from over 70 000 adults were collected in the UCL COVID-19 Social Study. When including participants living in England with three follow-up measures and no missing values, our analytic sample consisted of 36 520 participants. The average depression score was 6·6 (SD=6·0, range 0-27) and the average anxiety score 5·7 (SD=5·6, range 0-21) in week 1. Anxiety and depression levels both declined across the first 20 weeks following the introduction of lockdown in England (b=-1·93, SE=0·26, p<0·0001 for anxiety; b=-2·52, SE=0·28, p<0·0001 for depressive symptoms). The fastest decreases were seen across the strict lockdown period (between weeks 2 and 5), with symptoms plateauing as further lockdown easing measures were introduced (between weeks 16 and 20). Being a woman or younger, having lower educational attainment, lower income, or pre-existing mental health conditions, and living alone or with children were all risk factors for higher levels of anxiety and depression at the start of lockdown. Many of these inequalities in experiences were reduced as lockdown continued, but differences were still evident 20 weeks after the start of lockdown. INTERPRETATION: These data suggest that the highest levels of depression and anxiety occurred in the early stages of lockdown but declined fairly rapidly, possibly because individuals adapted to circumstances. Our findings emphasise the importance of supporting individuals in the lead-up to future lockdowns to try to reduce distress, and highlight that groups already at risk for poor mental health before the pandemic have remained at risk throughout lockdown and its aftermath. FUNDING: Nuffield Foundation, UK Research and Innovation, Wellcome Trust.


Subject(s)
Adaptation, Psychological , Anxiety Disorders/epidemiology , Anxiety/epidemiology , COVID-19 , Depression/epidemiology , Depressive Disorder/epidemiology , Physical Distancing , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , England/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Psychological Distress , Risk , Time Factors , Young Adult
13.
Respir Physiol Neurobiol ; 288: 103644, 2021 06.
Article in English | MEDLINE | ID: covidwho-1121917

ABSTRACT

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV1 (p = 0.04), DLCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower DLCO, reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19.


Subject(s)
COVID-19/complications , Dyspnea/physiopathology , Exercise Tolerance , Fatigue/physiopathology , Pulmonary Gas Exchange , Spirometry , Adult , Aged , COVID-19/physiopathology , Chronic Disease , Dyspnea/blood , Female , Forced Expiratory Volume , Functional Status , Humans , Male , Middle Aged , Oxygen/blood , Respiratory Function Tests , SARS-CoV-2 , Severity of Illness Index , Survivors , Vital Capacity , Walk Test
14.
PLoS One ; 16(3): e0247999, 2021.
Article in English | MEDLINE | ID: covidwho-1119474

ABSTRACT

PURPOSE: The Covid-19 pandemic has brought unprecedented stress to students and educational institutions across the world. We aimed to estimate the effect of the pandemic on the mental health of college students. METHODS: We used data on 419 first-year students (ages 18-20) at a large public university in North Carolina both before (October 2019-February 2020) and after (June/July 2020) the start of the Covid-19 pandemic. After evaluating descriptive data on mental health and stressors by students' demographic characteristics, we estimated the associations between Covid-19 stressors (including work reductions, health, distanced learning difficulties and social isolation) and mental health symptoms and severity controlling for students' pre-pandemic mental health, psychosocial resources, and demographic characteristics. RESULTS: We found that the prevalence of moderate-severe anxiety increased from 18.1% before the pandemic to 25.3% within four months after the pandemic began; and the prevalence of moderate-severe depression increased from 21.5% to 31.7%. White, female and sexual/gender minority (SGM) students were at highest risk of increases in anxiety symptoms. Non-Hispanic (NH) Black, female, and SGM students were at highest risk of increases in depression symptoms. General difficulties associated with distanced learning and social isolation contributed to the increases in both depression and anxiety symptoms. However, work reductions as well as Covid-19 diagnosis and hospitalization of oneself, family members or friends were not associated with increases in depression or anxiety symptoms. CONCLUSION: Colleges may be able to reduce the mental health consequences of Covid-19 by investing in resources to reduce difficulties with distance learning and reduce social isolation during the pandemic.


Subject(s)
Anxiety/etiology , COVID-19 , Depression/etiology , Mental Health , Students , Adolescent , Adult , Anxiety/psychology , COVID-19/epidemiology , Depression/psychology , Education, Distance , Female , Humans , Longitudinal Studies , Male , North Carolina/epidemiology , Physical Distancing , Risk Factors , Social Isolation , Students/psychology , Universities , Young Adult
15.
Sci Rep ; 11(1): 3061, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1065953

ABSTRACT

The outbreak of COVID-19 has raised interest in the kinin-kallikrein system. Viral blockade of the angiotensin-converting enzyme 2 impedes degradation of the active kinin des-Arg(9)-bradykinin, which thus increasingly activates bradykinin receptors known to promote inflammation, cough, and edema-symptoms that are commonly observed in COVID-19. However, lean and reliable investigation of the postulated alterations is currently hindered by non-specific peptide adsorption, lacking sensitivity, and cross-reactivity of applicable assays. Here, an LC-MS/MS method was established to determine the following kinins in respiratory lavage fluids: kallidin, bradykinin, des-Arg(10)-kallidin, des-Arg(9)-bradykinin, bradykinin 1-7, bradykinin 2-9 and bradykinin 1-5. This method was fully validated according to regulatory bioanalytical guidelines of the European Medicine Agency and the US Food and Drug Administration and has a broad calibration curve range (up to a factor of 103), encompassing low quantification limits of 4.4-22.8 pg/mL (depending on the individual kinin). The application of the developed LC-MS/MS method to nasal lavage fluid allowed for the rapid (~ 2 h), comprehensive and low-volume (100 µL) determination of kinins. Hence, this novel assay may support current efforts to investigate the pathophysiology of COVID-19, but can also be extended to other diseases.


Subject(s)
Bradykinin/analysis , Kallikrein-Kinin System , Nasal Lavage Fluid/chemistry , Adult , COVID-19 , Chromatography, Liquid , Female , Healthy Volunteers , Humans , Male , Tandem Mass Spectrometry , Young Adult
16.
Nat Biotechnol ; 39(6): 717-726, 2021 06.
Article in English | MEDLINE | ID: covidwho-1065901

ABSTRACT

Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , RNA, Messenger/pharmacology , SARS-CoV-2/genetics , Animals , COVID-19/genetics , COVID-19/virology , CRISPR-Cas Systems/genetics , Cricetinae , Disease Models, Animal , Humans , Influenza, Human/genetics , Influenza, Human/virology , Mice , Orthomyxoviridae/drug effects , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , RNA, Messenger/genetics , RNA, Viral/genetics , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2/pathogenicity
17.
J Inflamm Res ; 13: 1219-1243, 2020.
Article in English | MEDLINE | ID: covidwho-1054929

ABSTRACT

PURPOSE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has grown into a pandemic and without a specific cure, disease management is the need of the hour through symptomatic interventions. Studies with severe acute respiratory syndrome-coronavirus (SARS-CoV) have highlighted the role of herbal medicines either in combination with antiviral drugs or by themselves in curtailing the severity of infection and associated inflammation. Divya-Swasari-Vati is an Indian ayurvedic formulation used in the treatment of chronic cough and lung inflammation, which is one of the first symptoms of SARS-CoV-2 infections. METHODS: In this study, we used a A549 cell xenotransplant in the swim bladder of zebrafish and modeled the SARS-CoV-2 infection by injecting the fish with a recombinant spike protein. The different groups were given normal feed or feed mixed with either dexamethasone (as the control drug) or Divya-Swasari-Vati. The changes in behavioral fever, infiltration of pro-inflammatory cells in the swim bladder, degeneration or presence of necrotic cells in the kidney, and gene expression of pro-inflammatory cytokines were studied to determine the rescue of the diseased phenotype. RESULTS: Challenge with the spike protein caused changes in the swim bladder cytology with infiltrating pro-inflammatory cells, skin hemorrhage, and increase in behavioral fever. This was also accompanied by increased mortality of the disease control fish. Treatment with Divya-Swasari-Vati reversed most of the disease symptoms including damage to the kidney glomerulocytes, and complete reversal of behavioral fever. Dexamethasone, used as a comparator, was only able to partly rescue the behavioral fever phenotype. Divya-Swasari-Vati also suppressed the pro-inflammatory cytokines, IL-6 and TNF-α, levels in a dose-dependent manner, under in vivo and in vitro conditions. CONCLUSION: The study showed that the A549 xenotransplanted zebrafish injected with the recombinant spike protein of SARS-CoV-2 is an efficient model for the disease; and treatment with Divya-Swasari-Vati medicine rescued most of the inflammatory damage caused by the viral spike protein while increasing survival of the experimental fish.

18.
J Med Internet Res ; 22(11): e22407, 2020 11 23.
Article in English | MEDLINE | ID: covidwho-979790

ABSTRACT

BACKGROUND: The internet is a well-known source of information that patients use to better inform their opinions and to guide their conversations with physicians during clinic visits. The novelty of the recent COVID-19 outbreak has led patients to turn more frequently to the internet to gather more information and to alleviate their concerns about the virus. OBJECTIVE: The aims of the study were to (1) determine the most commonly searched phrases related to COVID-19 in the United States and (2) identify the sources of information for these web searches. METHODS: Search terms related to COVID-19 were entered into Google. Questions and websites from Google web search were extracted to a database using customized software. Each question was categorized into one of 6 topics: clinical signs and symptoms, treatment, transmission, cleaning methods, activity modification, and policy. Additionally, the websites were categorized according to source: World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), non-CDC government, academic, news, and other media. RESULTS: In total, 200 questions and websites were extracted. The most common question topic was transmission (n=63, 31.5%), followed by clinical signs and symptoms (n=54, 27.0%) and activity modification (n=31, 15.5%). Notably, the clinical signs and symptoms category captured questions about myths associated with the disease, such as whether consuming alcohol stops the coronavirus. The most common websites provided were maintained by the CDC, the WHO, and academic medical organizations. Collectively, these three sources accounted for 84.0% (n=168) of the websites in our sample. CONCLUSIONS: In the United States, the most commonly searched topics related to COVID-19 were transmission, clinical signs and symptoms, and activity modification. Reassuringly, a sizable majority of internet sources provided were from major health organizations or from academic medical institutions.


Subject(s)
Coronavirus Infections , Health Education/statistics & numerical data , Internet/statistics & numerical data , Pandemics , Pneumonia, Viral , Search Engine/statistics & numerical data , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , SARS-CoV-2 , United States/epidemiology
19.
Curr Pharm Des ; 27(9): 1185-1193, 2021.
Article in English | MEDLINE | ID: covidwho-976088

ABSTRACT

SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, chloroquine and hydroxychloroquine, against SARS-CoV-2, have shown to be a potential area of interest for drug development due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discussed analogs of the drugs to understand the quinoline scaffold's potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways, primarily through the modification of its substituents. We studied these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle, pre and post entry. In this study, we reviewed chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of viruses. Furthermore, we reviewed the compound's potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to chloroquine can act as antivirals or attenuate symptoms through the stimulation of the host immune system or reduction of oxidative stress. Furthermore, we discuss perspectives of the drug's repurposing due to its ability to inhibit the beta-hematin formation and to be a Zinc Ionophore.


Subject(s)
COVID-19 , Chloroquine , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/pharmacology , Humans , SARS-CoV-2
20.
Phytother Res ; 34(12): 3137-3147, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-969744

ABSTRACT

At the end of 2019, a novel flu-like coronavirus named COVID-19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID-19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID-19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID-19 through the inhibition of COVID-19 main protease, 3-chymotrypsin-like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID-19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Flavanones/therapeutic use , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/metabolism , Flavanones/pharmacology , Humans , SARS-CoV-2/drug effects
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