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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335706

ABSTRACT

Background: The systemic inflammatory response following severe coronavirus infection (COVID-19) is associated with poor outcome. Several anti-inflammatory medications were studied in COVID-19 patients. Xanthohumol (Xn), a natural extract from hop cones, possesses strong anti-inflammatory and antioxidative properties. The aim of this study was to analyse the effect of Xn on the inflammatory response and the clinical outcome of COVID-19 patients. Methods Adult patients treated for acute respiratory failure (PaO 2 /FiO 2 less than 150) were studied. Patients were randomized into two groups: Xn – patients receiving adjuvant treatment with Xn at a daily dose of 4.5 mg/kg body weight for 7 days, and C – controls (patients receiving placebo – NaCl 0.9%). Observations were performed at four time points: immediately after admission to the ICU and on the 3rd, 5th and 7th days of treatment. The inflammatory response was assessed based on the plasma IL-6 concentration, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP) and D-dimer levels. The mortality rate was determined 28 days after admission to the ICU. Results Seventy-two patients were eligible for the study, and 50 were included in the final analysis. The mortality rate was significantly lower and the clinical course was shorter in the Xn group compared to controls (20% vs. 48%, p < 0.05, and 9 ± 3 days vs. 22 ± 8 days, p < 0.001). Treatment with Xn decreased plasma IL-6 concentration (p < 0.01), D-dimer levels (p < 0.05) and NLR (p < 0.01) more significantly compared to standard treatment. Conclusion Adjuvant therapy with Xn appears to be a promising anti-inflammatory treatment in COVID-19 patients.

2.
J Med Virol ; 94(6): 2402-2413, 2022 06.
Article in English | MEDLINE | ID: covidwho-1718416

ABSTRACT

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.


Subject(s)
COVID-19 , Asia , COVID-19/epidemiology , Europe/epidemiology , Humans , SARS-CoV-2 , Socioeconomic Factors
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329032

ABSTRACT

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Hubei province of China in December 2019 and spread rapidly to other parts of the world, causing the coronavirus disease 2019 (COVID-19). The angiotensin-converting enzyme-2 (ACE2) is recognized as the host receptor used by the SARS-CoV-2 virus to enter its target cells. Recent studies suggest that ACE2 gene polymorphisms might be candidates for genetic susceptibility of SARS-CoV-2 infection. The aim of the study was to evaluate the influence of ACE2 polymorphisms on COVID-19 disease risk and severity. Results In our study we confirmed that there is a statistically significant increased risk of a more severe disease course of SARS-CoV-2 infection associated with the need for hospitalization in the intensive care unit for patients with specific polymorphisms of the ACE2 gene. The most significant correlation was found for variant ACE2 rs2285666 (AA allele, OR=2.12, p=0.0189) and ACE2 rs2074192 (TT allele, OR=2.05, p=0.0016), and also for ACE2 rs4646174 (GG allele, OR=1.93, p=0.0016), ACE2 rs4646156 (TT allele OR=1.71, p=0.008) and ACE2 rs2158083 (TT allele OR=1.84, p=0.0025). Conclusions In conclusion, our findings identify that certain ACE2 polymorphisms impact the severity of COVID-19 disease independently of other well-known risk factors.

4.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1690192

ABSTRACT

In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319046

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is spreading at an alarming rate globally. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and many known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR=0.85, 95% CI=(0.02, 3.93), P =0.762] and lower risk of death [(HR= 0.76;95% CI=(0.16, 3.72), P =0.735)];however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR=0.96, 95% CI=(0.61–2.99), P =0.942] and patients on statins had a more normal computed tomography (CT) scan result [OR=0.41, 95% CI= (0.07–2.33), P =0.312]. Conclusions: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19 , we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

6.
Int J Environ Res Public Health ; 19(3)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1643600

ABSTRACT

BACKGROUND: Due to the unpredictable nature of COVID-19, there is a need to identify patients at high risk of severe course of the disease and a higher mortality rate. OBJECTIVE: This study aims to find the correlation between frailty and mortality in adult, hospitalized patients with COVID-19. METHODS: Clinical records of 201 patients who suffered from COVID-19 and were hospitalized between October 2020 and February 2021 were retrospectively analyzed. Demographic, clinical, and biochemical data were collected. Patients were assessed using Clinical Frailty Scale (CFS) and were divided into three groups: CFS 1-3 fit; CFS 4-6 vulnerable and with mild to moderate frailty; CSF 7-9, severe frailty. The association between frailty and in-hospital mortality was the primary outcome. RESULTS: Severe frailty or terminal illness was observed in 26 patients (12.94%) from a cohort of 201 patients. Those patients were older (median age 80.73, p < 0.001) and had more comorbidities. Frailty was also associated with higher requirement for oxygen supplementation, greater risk of in-hospital complications and worse biochemical laboratory results. An increase in CFS score also correlated with higher mortality (OR = 1.89, p < 0.001). The Conclusions: Clinical Frailty Scale (CFS) can be used as a potentially useful tool in predicting mortality in patients with COVID-19.


Subject(s)
COVID-19 , Fatigue Syndrome, Chronic , Frailty , Adult , Aged , Aged, 80 and over , Cohort Studies , Frail Elderly , Humans , Prognosis , Retrospective Studies , SARS-CoV-2
7.
Drug Resist Updat ; 59: 100794, 2021 12.
Article in English | MEDLINE | ID: covidwho-1561685

ABSTRACT

The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Adult , Antiviral Agents/therapeutic use , COVID-19/therapy , Humans , Immunization, Passive , Lactams , Leucine , Nitriles , Pandemics , Proline , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
8.
Intensive Care Med ; 47(10): 1089-1103, 2021 10.
Article in English | MEDLINE | ID: covidwho-1359936

ABSTRACT

Delirium is the most common manifestation of brain dysfunction in critically ill patients. In the intensive care unit (ICU), duration of delirium is independently predictive of excess death, length of stay, cost of care, and acquired dementia. There are numerous neurotransmitter/functional and/or injury-causing hypotheses rather than a unifying mechanism for delirium. Without using a validated delirium instrument, delirium can be misdiagnosed (under, but also overdiagnosed and trivialized), supporting the recommendation to use a monitoring instrument routinely. The best-validated ICU bedside instruments are CAM-ICU and ICDSC, both of which also detect subsyndromal delirium. Both tools have some inherent limitations in the neurologically injured patients, yet still provide valuable information about delirium once the sequelae of the primary injury settle into a new post-injury baseline. Now it is known that antipsychotics and other psychoactive medications do not reliably improve brain function in critically ill delirious patients. ICU teams should systematically screen for predisposing and precipitating factors. These include exacerbations of cardiac/respiratory failure or sepsis, metabolic disturbances (hypoglycemia, dysnatremia, uremia and ammonemia) receipt of psychoactive medications, and sensory deprivation through prolonged immobilization, uncorrected vision and hearing deficits, poor sleep hygiene, and isolation from loved ones so common during COVID-19 pandemic. The ABCDEF (A2F) bundle is a means to facilitate implementation of the 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS) Guidelines. In over 25,000 patients across nearly 100 institutions, the A2F bundle has been shown in a dose-response fashion (i.e., greater bundle compliance) to yield improved survival, length of stay, coma and delirium duration, cost, and less ICU bounce-backs and discharge to nursing homes.


Subject(s)
COVID-19 , Delirium , Adult , Critical Care , Critical Illness , Delirium/diagnosis , Delirium/etiology , Delirium/therapy , Humans , Intensive Care Units , Pandemics , SARS-CoV-2
9.
J Clin Med ; 10(13)2021 Jul 02.
Article in English | MEDLINE | ID: covidwho-1295866

ABSTRACT

Delirium is a sign of deterioration of homeostasis and worse prognosis. The aim of this study was to investigate the frequency, risk factors and prognosis of delirium in patients with COVID-19 in a temporary acute setting hospital. A retrospective cohort analysis of data collected between October 2020 and February 2021 from two temporary acute care hospitals was performed. All consecutive hospitalized patients ≥18 years old with COVID-19 were included. An assessment of consciousness was carried out at least two times a day, including neurological examination. Delirium was identified through retrospective chart review according to DSM-5 criteria if present at least once during hospitalization. Analysis included 201 patients, 39 diagnosed with delirium (19.4%). Delirious patients were older (p < 0.001), frailer (p < 0.001) and the majority were male (p = 0.002). Respiratory parameters were worse in this group with higher oxygen flow (p = 0.013), lower PaO2 (p = 0.043) and higher FiO2 (p = 0.006). The mortality rate was significantly higher in patients with delirium (46.15% vs 3.70%, p < 0.001) with OR 17.212 (p < 0.001) corrected for age and gender. Delirious patients experienced significantly more complications: cardiovascular (OR 7.72, p < 0.001), pulmonary (OR 8.79, p < 0.001) or septic (OR 3.99, p = 0.029). The odds of mortality in patients with COVID-19 presenting with delirium at any point of hospitalization were seventeen times higher.

10.
Int J Environ Res Public Health ; 18(4)2021 02 23.
Article in English | MEDLINE | ID: covidwho-1100117

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic and a burden to global health at the turn of 2019 and 2020. No targeted treatment for COVID-19 infection has been identified so far, thus supportive treatment, invasive and non-invasive oxygen support, and corticosteroids remain a common therapy. High-flow nasal cannula (HFNC), a non-invasive oxygen support method, has become a prominent treatment option for respiratory failure during the SARS-CoV-2 pandemic. HFNC reduces the anatomic dead space and increases positive end-expiratory pressure (PEEP), allowing higher concentrations and higher flow of oxygen. Some studies suggest positive effects of HFNC on mortality and avoidance of intubation. Spontaneous pneumothorax has been observed in patients suffering from SARS-CoV-2 pneumonia. Although the viral infection itself contributes to its development, higher PEEP generated by both HFNC and mechanical ventilation is another risk factor for increased alveoli damage and air-leak. Herein, we present three cases of patients with no previous history of lung diseases who were diagnosed with COVID-19 viral pneumonia. All of them were supported with HFNC, and all of them presented spontaneous pneumothorax.


Subject(s)
COVID-19 , Oxygen Inhalation Therapy/adverse effects , Pneumothorax , Respiratory Insufficiency , Aged, 80 and over , Cannula , Humans , Intensive Care Units , Male , Middle Aged , Pneumothorax/epidemiology , Pneumothorax/etiology , Pneumothorax/therapy , Respiratory Insufficiency/therapy
11.
Transl Med Commun ; 6(1): 3, 2021.
Article in English | MEDLINE | ID: covidwho-1045590

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. RESULTS: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61-2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07-2.33), P = 0.312]. CONCLUSIONS: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

12.
Pharmaceuticals (Basel) ; 14(1)2021 Jan 17.
Article in English | MEDLINE | ID: covidwho-1031152

ABSTRACT

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

14.
Clin Interv Aging ; 15: 1231-1240, 2020.
Article in English | MEDLINE | ID: covidwho-689982

ABSTRACT

Since the beginning of 2020, the whole world has been struggling with the pandemic of Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7). Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs. Individualized treatment decisions should be based on the clinical condition and co-morbidities of each patient.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Aged , Animals , COVID-19 , Comorbidity , Coronavirus Infections/genetics , Eye Diseases, Hereditary , Gene Frequency , Genotype , Humans , Pandemics , Pneumonia, Viral/genetics , Retinal Diseases , SARS-CoV-2
15.
Brain Sciences ; 10(7):465, 2020.
Article | WHO COVID | ID: covidwho-651559

ABSTRACT

Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache. The exact mechanisms of headache and myalgia during viral infection are still unknown. Moreover, many patients with respiratory failure get admitted to the intensive care unit (ICU) for ventilatory support. Pain in ICU patients can be associated with viral disease itself (myalgia, arthralgia, peripheral neuropathies), may be caused by continuous pain and discomfort associated with ICU treatment, intermittent procedural pain and chronic pain present before admission to the ICU. Undertreatment of pain, especially when sedation and neuromuscular blocking agents are used, prone positioning during mechanical ventilation or extracorporeal membrane oxygenation (ECMO) may trigger delirium and cause peripheral neuropathies. This narrative review summarizes current knowledge regarding challenges associated with pain assessment and management in COVID-19 patients. A structured prospective evaluation should be undertaken to analyze the probability, severity, sources and adequate treatment of pain in patients with COVID-19 infection.

16.
Drug Resist Updat ; 53: 100719, 2020 12.
Article in English | MEDLINE | ID: covidwho-645153

ABSTRACT

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Approval/methods , SARS-CoV-2/drug effects , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/metabolism , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/metabolism , Antimalarials/administration & dosage , Antimalarials/metabolism , Antiviral Agents/metabolism , COVID-19/metabolism , Clinical Trials as Topic/methods , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/metabolism , Drug Therapy, Combination , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/metabolism , SARS-CoV-2/metabolism , United States/epidemiology
17.
J Clin Med ; 9(6)2020 Jun 19.
Article in English | MEDLINE | ID: covidwho-609200

ABSTRACT

In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients' quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.

18.
Anaesthesiol Intensive Ther ; 52(2): 132-138, 2020.
Article in English | MEDLINE | ID: covidwho-291501

ABSTRACT

In March 2020, the World Health Organisation announced the COVID-19 pandemic caused by the SARS-CoV-2 virus. As well as respiratory failure, the SARS-CoV-2 may cause central nervous system (CNS) involvement, including delirium occurring in critically ill patients (ICU delirium). Due attention must be paid to this subject in the face of the COVID-19 pandemic. Delirium, the detection of which takes less than two minutes, is frequently underestimated during daily routine ICU care, but it may be a prodromal symptom of infection or hypoxia associated with severe respiratory failure. During the COVID-19 pandemic, systematic delirium monitoring using validated tests (CAM-ICU or ICDSC) may be sacrificed. This is likely to be due to the fact that the main emphasis is placed on organisational issues, i.e. the lack of ventilators, setting priorities for limited mechanical ventilation options, and a shortage of personal protective equipment. Early identification of patients with delirium is critical in patients with COVID-19 because the occurrence of delirium may be an early symptom of worsening respiratory failure or of infectious spread to the CNS mediated by potential neuroinvasive mechanisms of the coronavirus. The purpose of this review is to identify problems related to the development of delirium during the COVID-19 epidemic, which are presented in three areas: i) factors contributing to delirium in COVID-19, ii) potential pathophysiological factors of delirium in COVID-19, and iii) long-term consequences of delirium in COVID-19. This article discusses how healthcare workers can reduce the burden of delirium by identifying potential risk factors and difficulties during challenges associated with SARS-CoV-2 infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Delirium/etiology , Intensive Care Units , Pneumonia, Viral/complications , COVID-19 , Delirium/diagnosis , Delirium/prevention & control , Delirium/psychology , Humans , Pandemics , SARS-CoV-2
19.
J Clin Med ; 9(5)2020 May 11.
Article in English | MEDLINE | ID: covidwho-232697

ABSTRACT

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.

20.
Crit Care ; 24(1): 176, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-133387

ABSTRACT

The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Delirium/therapy , Intensive Care Units , Pneumonia, Viral/complications , COVID-19 , Coronavirus Infections/epidemiology , Delirium/etiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Safety
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