Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19:A Consensus Statement Based on Available Clinical Trials

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19

Επίδραση διαφορετικών κατηγοριών αντιυπερτασικών φαρμάκων στη μεταβλητότητα της αρτηριακής πίεσης και την ασυμπτωματική βλάβη οργάνων στόχων

INTRODUCTION: Blood pressure (BP) variability (BPV) is an inherent characteristic of BP and can be short-term (within 24 hours, from minute-to-minute to day/night variations, e.g., BP nocturnal dipping and morning surge), mid-term (over days), and long-term (over weeks, months, seasons, or years, including BPV among clinic/office visits) assessed with ambulatory (ABP), home (HBP), and office BP (OBP) measurements, respectively. All types of BPV are associated with adverse cardiovascular outcomes and the optimal treatment strategy regarding BPV is inadequately investigated. AIM: The aim of the REducing blood pressure Variability in Essential hypertension with RAmipril vErsus Nifedipine GITS Trial (REVERENT) was to compare a dihydropyridine calcium channel blocker (nifedipine gastrointestinal therapeutic system [GITS]) vs an angiotensin converting enzyme inhibitor (ramipril) on different BPV indices and related hypertension mediated preclinical organ damage (HMOD), independent of the average BP reduction. MATERIAL AND METHOD: This was a multicentre (three sites), international (China, Greece, Italy), prospective, randomized, open-label, blinded-end point study (PROBE) with 2 active treatment arms (Main Study duration 10 weeks), followed by open extension phase (Extension Study, overall duration of both phases 1 year. Adults with essential hypertension not receiving antihypertensive treatment were randomized to receive nifedipine GITS 30 mg or ramipril 10 mg and followed for 10 weeks (Main Study) or 1 year (Extension Study). Average BP, BPV and HMOD [carotid-femoral pulse wave velocity (cfPWV), albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI)] indices were compared during two to four occasions during the study follow-up. BPV was assessed using standard deviation (SD) and coefficient of variation (CV).RESULTS: Regarding the Main Study, 151 individuals were analyzed (mean age 53±10 [SD] years, males 58%, China/Greece/Italy 44/36/20%, baseline systolic OBP, HBP and 24h ABP 144±9, 138±10, and 143±10 mmHg, respectively). Regarding the Extension Study, 137 individuals were analyzed (mean age 52±10 years, males 61%, China/Greece/Italy 44/36/20%, baseline systolic OBP, HBP and 24h ABP 144±9, 137±10, and 143±10 mmHg, respectively). Average BP was reduced by all methods, with OBP presenting the largest reduction (20±13/10±7 mmHg systolic/diastolic baseline minus after 1 year of antihypertensive treatment, P<0.01). Average BP decline tended to be larger in the ramipril arm. BPV assessed with SD presented a reduction within the Main Study and then a gradual increase during the Extension Study for office BPV (-0.5±5.2/-0.3±2.5 mmHg, P=NS). Home BPV presented a large reduction (4.7±3.2/2.1±2.2 mmHg), while all aspects of ambulatory BPV did not show significant changes (-0.1±3.7/-0.1±2.4 mmHg for 24-hour weighted SD, P=NS), although there was a trend towards a decrease in ambulatory BPV with nifedipine and increase with ramipril. BPV assessed with CV presented a large decrease for HBP (3.0±2.4/2.1±2.7 mmHg, P<0.01) and an increase of different magnitude for all other methods of measurement. Home CV decrease was similar with both nifedipine and ramipril (3.0±2.2 vs 3.0±2.5 mmHg, respectively for systolic BPV, P=NS); while BPV increase in the other methods was generally larger and reached statistical significance in most cases for ramipril. The achieved BPV was consistently lower in the nifedipine arm. Regarding the HMOD indices, cfPWV, ACR, eGFR, cIMT, and LVMI, all were reduced during follow-up. cfPWV was significantly reduced in all individuals (0.6±1.1 m/s, P<0.01) without difference between nifedipine and ramipril. ACR and LVMI were significantly reduced only in the ramipril arm, while cIMT was significantly reduced only in the nifedipine arm. The degree of treatment-induced changes in BPV was not associated with the degree of HMOD change (regression or progression).CONCLUSION: Nifedipine appeared to have more favorable effects on BPV changes than ramipril. No association of BPV changes with HMOD changes was observed within one year of treatment in this group of patients with low cardiovascular risk. Future research is needed to confirm the findings of the REVERENT trial.ΕΙΣΑΓΩΓΗ: Η μεταβλητότητα (ΜΑΠ) αποτελεί εγγενές χαρακτηριστικό της αρτηριακής πίεσης (ΑΠ) και μπορεί να είναι βραχυπρόθεσμη (εντός 24 ωρών, από λεπτό σε λεπτό έως διακυμάνσεις ημέρας/νύχτας, π.χ. νυχτερινή πτώση και πρωινή αύξηση της ΑΠ), μεσοπρόθεσμη (μεταξύ ημερών), και μακροπρόθεσμη (μεταξύ εβδομάδων, μηνών, εποχών, ετών, και επισκέψεων στο ιατρείο) και εκτιμάται με μετρήσεις στην 24ωρη καταγραφή (ABP), στο σπίτι (HBP), και στο ιατρείο (OBP), αντίστοιχα. Όλες οι κατηγορίες ΜΑΠ συσχετίζονται με δυσμενή καρδιαγγειακή έκβαση ενώ οι θεραπευτικές παρεμβάσεις που στοχεύουν στην ΜΑΠ δεν είναι επαρκώς μελετημένες. ΣΚΟΠΟΣ: Ο σκοπός της μελέτης REducing blood pressure Variability in Essential hypertension with RAmipril vErsus Nifedipine GITS Trial (REVERENT) ήταν η σύγκριση της επίδρασης ενός διυδροπυριδινικού ανταγωνιστή διαύλων ασβεστίου (νιφεδιπίνη gastrointestinal therapeutic system [GITS]) έναντι ενός αναστολέα του μετατρεπτικού ενζύμου της αγγειοτασίνης (ραμιπρίλη) σε δείκτες ΜΑΠ και σε δείκτες ασυμπτωματικής βλάβης οργάνων-στόχων, μετά από διόρθωση για την επίδραση της μέσης πτώσης της ΑΠ. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΣ: Πρόκειται για πολυκεντρική (3 κέντρα), διεθνή (Ελλάδα, Ιταλία, Κίνα), προοπτική, τυχαιοποιημένη, ανοικτής επισήμανσης, τυφλού καταληκτικού σημείου μελέτη (PROBE) με 2 ενεργές θεραπευτικές ομάδες (Κύρια Μελέτη διάρκειας 10 εβδομάδων), που ακολουθείται από φάση ανοικτής επέκτασης (Μελέτη Επέκτασης με συνολική διάρκεια και των 2 φάσεων ενός έτους). Ενήλικες με ιδιοπαθή υπέρταση που δε λάμβαναν θεραπεία τυχαιοποιήθηκαν σε νιφεδιπίνη GITS 30mg ή ραμιπρίλη 10mg και παρακολουθήθηκαν για 10 εβδομάδες (Κύρια Μελέτη) ή ένα έτος (Μελέτη Επέκτασης). Η μέση ΑΠ, ΜΑΠ και οι βλάβες οργάνων-στόχων [καρωτιδομηριαία ταχύτητα σφυγμικού κύματος (cfPWV), λόγος αλβουμίνης προς κρεατινίνη (ACR), υπολογιζόμενος ρυθμός σπειραματικής διήθησης (eGFR), πάχος έσω-μέσω χιτώνα καρωτίδων (cIMT), και δείκτης μάζας αριστερής κοιλίας (LVMI)] συγκρίθηκαν μεταξύ δύο έως τεσσάρων επισκέψεων της μελέτης. Η ΜΑΠ εκτιμήθηκε με την τυπική απόκλιση (SD) και το συντελεστή μεταβλητότητας (CV). ΑΠΟΤΕΛΕΣΜΑΤΑ: Στην Κύρια Μελέτη, 151 άτομα αναλύθηκαν (μέση ηλικία 53±10 [SD] έτη, άρρενες 58%, Ελλάδα/Ιταλία/Κίνα 36/20/44%, αρχική συστολική OBP, HBP και 24ωρη ABP 144±9, 138±10, και 143±10 mmHg, αντίστοιχα). Στην Μελέτη Επέκτασης, 137 άτομα αναλύθηκαν (μέση ηλικία 52±10 years, άρρενες 61%, Ελλάδα/Ιταλία/Κίνα 36/20/44%, αρχική συστολική OBP, HBP και 24ωρη ABP 144±9, 137±10, και 143±10 mmHg, αντίστοιχα). Η μέση ΑΠ μειώθηκε με όλες τις μεθόδους, με την OBP να παρουσιάζει τη μεγαλύτερη πτώση (20±13/10±7 mmHg συστολική/διαστολική αρχική ΑΠ μείον ΑΠ μετά από ένα έτος θεραπείας, P<0.01). Η πτώση ΑΠ είχε την τάση να είναι μεγαλύτερη στο σκέλος της ραμιπρίλης. Η ΜΑΠ εκτιμώμενη με SD παρουσίασε πτώση κατά τη διάρκεια της Κύριας Μελέτης και σταδιακή αύξηση κατά τη διάρκεια της Μελέτης Επέκτασης για την ΜΑΠ ιατρείου (-0.5±5.2/-0.3±2.5 mmHg, P=NS). Η ΜΑΠ στο σπίτι παρουσίασε μεγάλη πτώση (4.7±3.2/2.1±2.2 mmHg), ενώ όλα τα είδη ΜΑΠ στην 24ωρη καταγραφή δεν παρουσίασαν σημαντικές αλλαγές (-0.1±3.7/-0.1±2.4 mmHg για το σταθμισμένο SD της 24ωρης ΑΠ, P=NS), παρά το γεγονός ότι παρατηρήθηκε τάση μείωσης με τη νιφεδιπίνη και αύξησης με τη ραμιπρίλη. Η ΜΑΠ εκτιμώμενη με CV παρουσίασε μεγάλη πτώση για το HBP (3.0±2.4/2.1±2.7 mmHg, P<0.01) και αύξηση διαφορετικού μεγέθους για όλες τις άλλες μεθόδους μέτρησης. Η πτώση του CV για την ΜΑΠ στο σπίτι ήταν παρόμοια για τα σκέλη νιφεδιπίνης και ραμιπρίλης (3.0±2.2 συγκριτικά με 3.0±2.5 mmHg, αντίστοιχα, για τη συστολική ΜΑΠ, P=NS), ενώ η αύξηση της ΜΑΠ με τις άλλες μεθόδους ήταν γενικά μεγαλύτερη και στατιστικά σημαντική στο σκέλος της ραμιπρίλης. Η επιτευχθείσα ΜΑΠ κατά τη διάρκεια της παρακολούθησης ήταν σταθερά χαμηλότερη στο σκέλος της νιφεδιπίνης. Σχετικά με τις βλάβες οργάνων-στόχων, τα cfPWV, ACR, eGFR, cIMT, και LVMI μειώθηκαν σημαντικά κατά τη διάρκεια της παρακολούθησης. Το cfPWV μειώθηκε σημαντικά σε όλους τους συμμετέχοντες (0.6±1.1 m/s, P<0.01), χωρίς διαφορά μεταξύ νιφεδιπίνης και ραμιπρίλης. Τα ACR και LVMI μειώθηκαν σημαντικά μόνο στα άτομα υπό ραμιπρίλη, ενώ το cIMT μειώθηκε σημαντικά μόνο στα άτομα υπό νιφεδιπίνη. Οι μεταβολές της ΜΑΠ μετά τη θεραπεία δεν σχετίστηκαν με τις μεταβολές των βλαβών οργάνων-στόχων (υποστροφή ή εξέλιξη). ΣΥΜΠΕΡΑΣΜΑΤΑ: Η νιφεδιπίνη παρουσίασε ευνοϊκότερη επίδραση στη ΜΑΠ συγκριτικά με τη ραμιπρίλη. Δεν αναδείχθηκε συσχέτιση μεταξύ των μεταβολών της ΜΑΠ και των μεταβολών των βλαβών οργάνων-στόχων μετά από ένα έτος θεραπείας στους συμμετέχοντες της παρούσας μελέτης που αποτελούν χαμηλού καρδιαγγειακού κινδύνου δείγμα. Χρειάζεται περαιτέρω έρευνα στο μέλλον για την επιβεβαίωση των ευρημάτων της μελέτης REVERENT

Επίπτωση και παράγοντες κινδύνου για εμφύτευση Μόνιμου βηματοδότη σε παιδιά μετά από καρδιοχειρουργικές επεμβάσεις

Εισαγωγή:Οι προγνωστικοί παράγοντες της Μόνιμης Βηματοδότησης (ΜΒ) μετά από καρδιοχειρουργικές επεμβάσεις στα παιδιά που απαιτούν προσωρινή μετεγχειρητική βηματοδότηση δεν έχουν μελετηθεί σε βάθος. Σκοπός: Σκοπός της μελέτης ήταν η εκτίμηση της επίπτωσης της ΜΒ στα παιδιά μετά από καρδιοχειρουργικές επεμβάσεις και των παραγόντων κινδύνου για την εμφύτευση ΜΒ. Υλικό και Μέθοδος:Μελετήθηκαν αναδρομικά ασθενείς &lt;18 ετών που υποβλήθηκαν σε Καρδιοχειρουργικές επεμβάσεις στο Ωνάσειο Καρδιοχειρουργικό Κέντρο την περίοδο 2002-2020. Οι ασθενείς που χρειάστηκαν μετεγχειρητική βηματοδότηση χωρίστηκαν σε δύο ομάδες: 1) Μόνιμους, όταν ελάμβαναν ΜΒ πριν το εξιτήριο και 2) Παροδικούς όταν δεν ελάμβαναν σύστημα ΜΒ. Συγκρίθηκαν τα δημογραφικά στοιχεία, τα ανατομικά χαρακτηριστικά και τα περιεγχειρητικά κλινικά χαρακτηριστικά προκειμένου να αναγνωρισθούν παράγοντες κινδύνου για την τοποθέτηση ΜΒ. Αποτελέσματα: Συνολικά 2.985 ασθενείς χειρουργήθηκαν και 286 (9,6%) βηματοδοτήθηκαν μετεγχειρητικά. Παροδική βηματοδότηση έλαβαν 245 (8,2%) ασθενείς και 41 (1,4%) έλαβαν ΜΒ. Η αποκατάσταση της προσωρινής βηματοδότησης συνέβη στο 91% των ασθενών της παροδικής ομάδας την 10η μετεγχειρητική ημέρα. Κατά την μονοπαραγοντική ανάλυση μεταβλητών, η τμηματική ανατομία {S, L, L}, η αυξημένη ηλικία και ο αριθμός των προηγούμενων χειρουργικών επεμβάσεων ήταν σημαντικοί παράγοντες κινδύνου για τοποθέτηση ΜΒ. Η ανάλυση πολλαπλής μεταβλητής λογιστικής παλινδρόμησης αναγνώρισε ότι οι επεμβάσεις για την αντιμετώπιση της απόφραξης στο χώρου εξόδου της αριστερής κοιλίας, αποτελούν ανεξάρτητο παράγοντα κινδύνου (OR: 6.27, 95% CI: 1,58-24.=,82, p=0,009). Συμπέρασμα: Η επίπτωση μετεγχειρητικών βραδυαρρυθμιών που απαιτούν προσωρινή και μόνιμη βηματοδότηση στο δείγμα της μελέτης μας ήταν παρόμοια με τα δημοσιευμένα δεδομένα. Ασθενείς με κολποκοιλιακή ασυμφωνία, πολλαπλές προηγούμενες χειρουργικές επεμβάσεις ή μετά από χειρουργικές επεμβάσεις στο χώρο εξόδου της αριστερής κοιλίας έχουν τη μεγαλύτερη πιθανότητα να χρειαστούν ΜΒ.Background:The predictors of permanent pacing after paediatric cardiac surgery who require temporary postoperative pacing are not well understood. Objectives: We sought to study a group of patients requiring postoperative pacing in a pediatric cardiac surgical unit in order to identify risk factors associated with Permanent Pacemaker (PPM) implantation. Material and Methods:We performed a retrospective analysis of patients under 18 years of age who required pacing after heart surgery from 2002 to 2020 using our Hospital records. Patients who required postoperative pacing were divided in two groups: 1) permanent, when a PPM was implanted before discharge or 2) transient, if PPM was not performed. Demographic characteristics, anatomic diagnosis and perioperative variables of the two groups were compared. Results:Overall, 2985 patients were operated and 286 (9.6%) received postoperative pacing. Temporary pacing was performed in 245 (8.2%) patients and PPM implantation was required in 41 (1.4%). Resolution of bradycardia occurred in 91 % of the patients in the transient group by postoperative day 10. On univariable analysis, segmental anatomy {S,L,L}, age and number of previous surgeries were significantly higher in the permanent group. Multivariable logistic regression analysis identified Left Ventricular Outflow Track (LVOT) operation for obstruction as an independent risk factor for permanent pacemaker implantation (OR:6.27, 95% CI: 1.58-24.82, p=0.009). Conclusions:The incidence of postoperative bradyarrhythmias requiring temporary and permanent pacing in our study population was similar to the published data. Patients with Atrio-Ventricular discordance, multiple previous surgeries or after LVOT operations are more likely to require permanent pacing

Clinical examination practices and perceptions in the era of COVID-19

Introduction The art of clinical examination has been the cornerstone of medical practices since ancient years. Recent technological achievements and their overuse have led falsely to underestimation of their significance, which has been further questioned during the coronavirus disease 2019 (COVID-19) pandemic, due to concerns regarding exposure risk and use of personal protective equipment. Areas covered The role of clinical examination (namely chest examination) during the pandemic is discussed. Emerging evidence is being accumulated concerning alternatives to traditional practices. Telemedicine stands out as a promising tool, allowing inspection and interaction between physicians and patients, proved to be useful for many medical specialties but not enough for some others. Medical practices cannot remain the same in the era of the COVID-19 pandemic, yet realistic strategies should be adopted for their optimal and safe implementation. Expert opinion The experiences of a dedicated Reference Center for COVID-19 along with a suggested algorithm for conducting clinical examinations are presented. According to our experience, an initial detailed clinical examination upon admission of each COVID-19 patient appears to be necessary. Then, vital signs and signs of respiratory distress using inspection should be checked frequently. A focused examination approach should be adopted, in case of new onset clinical problems

The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19

Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis

Background and aims: Statin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality. Methods: A systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus nonusers. Results: 22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 +/- 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58-100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Metaanalysis of 12 studies (n = 72,881, weighted age 65 +/- 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities. Conclusions: This meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients