SEROPREVALENCE and RISK FACTORS for SARS-CoV-2 among INCARCERATED ADULT MEN in QUEBEC

Background: People in prison are at increased risk of SARS-CoV-2 infection due to overcrowding and the challenges in implementing infection prevention and control measures;however, seroprevalence studies are lacking in correctional settings. We examined the seroprevalence of SARS-CoV-2 and associated modifiable risk factors among incarcerated adult men in Quebec, Canada. Methods: We conducted a cross-sectional seroprevalence study in three provincial prisons, representing 45% of Quebec's incarcerated male provincial population. The primary outcome was SARS-CoV-2 antibody seropositivity, detected by the Roche Elecsys® anti-SARS-CoV-2 serology test. Participants completed self-administered questionnaires on sociodemographic, clinical, and carceral characteristics. The association of carceral variables with SARS-CoV-2 seropositivity was examined using Poisson regression models with robust standard error. Crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95%CI) were calculated. Results: Between January 19 and September 15, 2021, 246 of 1,100 (22%) recruited individuals tested positive across three prisons (range 15-27%). Of these, 192 (78%) reported having at least one previous SARS-CoV-2 PCR test, with 122 (64%) testing positive and 70 (36%) testing negative;73 (30%) individuals with a positive serology test were asymptomatic. Seropositivity increased with time spent in prison since March 2020 (aPR 2.17, 95%CI 1.53-3.07 for all vs. little), employment during incarceration (aPR 1.64, 95%CI 1.28-2.11 vs. not), shared meal consumption during incarceration (with cellmates: aPR 1.46, 95%CI 1.08-1.97 vs. alone;with sector: aPR 1.34, 95%CI 1.03-1.74 vs. alone), and incarceration post-prison outbreak (aPR 2.32, 95% CI 1.69-3.18 vs. pre-outbreak) (see Table). Shared (vs. single) cells were not associated with increased seropositivity. Conclusion: The seroprevalence of SARS-CoV-2 among incarcerated individuals was high and varied between prisons. Several modifiable carceral factors were associated with seropositivity, underscoring the importance of decarceration and occupational safety measures, individual meal consumption, and enhanced infection prevention and control measures including vaccination during incarceration.

Management of renin-angiotensinaldosterone system blockade in patients admitted in hospital with confirmed coronavirus disease (Covid-19) infection: The mcgill raas-covid-19 randomized controlled trial

Background: More data is needed on the cardiovascular impact of discontinuing versus continuing renin-angiotensin aldosterone system inhibitors (RAASi) among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Methods: The McGill RAAS-COVID-19 trial was a randomized, open label trial in adult patients hospitalized with COVID-19, who were previously treated with RAASi (angiotensin converting enzyme inhibitors [ACEi]/angiotensin receptor blocker [ARB]) (NCT04508985;10/2020-03/2021). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]). All analyses were conducted using the intention-to-treat principle. Results: Overall, 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a similar mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5);p= 0.60), but the negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.7 [95% CI 1.1 to 2.6];p=0.03). Particularly, RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs.-27.5%;p= 0.02) and increased the incidence of acute heart failure (33% vs. 4.2%, p=0.03). Conclusion: Discontinuation of RAASi increased BNP levels and risk of acute heart failure in participants hospitalized with COVID-19;where possible, RAASi should be continued.

Potential drug-drug interactions in hospitalized COVID-19 patients (CATCO-DDI)

Background: Therapies for managing COVID-19 disease may interact with other drugs, particularly in hospitalized patients with comorbidities. Objectives: Characterize the prevalence of drug-drug interactions (DDIs) between investigational/approved medications for managing COVID-19 (COVID-meds) and co-medications (co-meds) in hospitalized COVID-19 patients. Methods: Multicentre retrospective observational study of hospitalized COVID-19 patients screened for the CATCO trial between 1-Apr-20 and 15-Sep-20. Patients' co-meds were assessed for potential DDIs with the following COVID-meds: hydroxychloroquine (HQ), lopinavir/ritonavir (LPV), remdesivir (REM), dexamethasone (DEX), azithromycin (AZ), interferon beta-1B (IFN) and tocilizumab (TOC). The Liverpool-COVID DDI website and Lexicomp were used to identify and characterize DDI severity (red: do not co-administer, amber: potential interaction) and potential clinical impact. QT prolongation risk was assessed with the Tisdale risk score. The primary outcome was the prevalence of subjects with =1 potential clinically significant (red/amber) DDI between each COVID-med and co-med. Secondary outcomes included DDI severity and potential clinical impact. Descriptive statistics are presented as medians (range) or proportions. Results: Data from 51 patients are available: 61% male, age 74 (44-95) years, 6 (1-15) comorbidities, Tisdale risk score 6 (31.4% moderate risk, 11.8% high risk) and 10 (0-19) co-meds. LPV had the highest rate of potential DDIs (92.2%, 45% red, 3 DDIs per patient) with risk of increased co-med toxicity (most commonly psychotropics, anticoagulants/antiplatelets), while REM and IFN had the least (2% and 9.6%, respectively). Most patients (75%) had =1 DEX DDI (mostly amber, 1per patient) with risk of increased co-med toxicity. The most common DDIs with HQ and AZ involved increased risk of QTc prolongation. Over one-third (35%) of patients were deemed ineligible for CATCO at screening due to DDIs with LPV. Conclusions: Hospitalized COVID-19 patients are at high risk of DDIs with many investigational/approved COVID medications. Routine DDI screening is recommended, ideally using both general and COVID-specific DDI resources.

Acute Kidney Injury and Renal Replacement Therapy in COVID-19 Versus Other Respiratory Viruses: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute kidney injury (AKI) is a potentially fatal complication of Coronavirus Disease-2019 (COVID-19). Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, to its viral receptor, angiotensin converting enzyme 2 (ACE2), results in viral entry and may cause AKI. OBJECTIVES: We performed a systematic review and meta-analysis of the frequencies of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients and compared those frequencies with patients who were infected by respiratory viruses that bind or downregulate ACE2 (ACE2-associated viruses) and viruses that do not bind nor downregulate ACE2 (non-ACE2-associated viruses). DESIGN: Systematic review and meta-analysis. SETTING: Observational studies on COVID-19 and other respiratory viral infections reporting AKI and RRT were included. The exclusion criteria were non-English articles, non-peer-reviewed articles, review articles, studies that included patients under the age of 18, studies including fewer than 10 patients, and studies not reporting AKI and RRT rates. PATIENTS: Adult COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza patients. MEASUREMENTS: We extracted the following data from the included studies: author, year, study location, age, sex, race, diabetes mellitus, hypertension, chronic kidney disease, shock, vasopressor use, mortality, intensive care unit (ICU) admission, ICU mortality, AKI, and RRT. METHODS: We systematically searched PubMed and EMBASE for articles reporting AKI or RRT. AKI was defined by authors of included studies. Critical illness was defined by ICU admission. We performed a random effects meta-analysis to calculate pooled estimates for the AKI and RRT rate within each virus group using a random intercept logistic regression model. RESULTS: Of 23 655 hospitalized, critically ill COVID-19 patients, AKI frequencies were not significantly different between COVID-19 patients (51%, 95% confidence interval [CI]: 44%-57%) and critically ill patients infected with ACE2-associated (56%, 95% CI: 37%-74%, P = .610) or non-ACE2-associated viruses (63%, 95% CI: 43%-79%, P = .255). Pooled RRT rates were also not significantly different between critically ill, hospitalized patients with COVID-19 (20%, 95% CI: 16%-24%) and ACE2-associated viruses (18%, 95% CI: 8%-33%, P = .747). RRT rates for both COVID-19 and ACE2-associated viruses were significantly different (P < .001 for both) from non-ACE2-associated viruses (49%, 95% CI: 44%-54%). After adjusting for shock or vasopressor use, AKI and RRT rates were not significantly different between groups. LIMITATIONS: Limitations of this study include the heterogeneity of definitions of AKI that were used across different virus studies. We could not match severity of infection or do propensity matching across studies. Most of the included studies were conducted in retrospective fashion. Last, we did not include non-English publications. CONCLUSIONS: Our findings suggest that viral ACE2 association does not significantly alter the rates of AKI and RRT among critically ill patients admitted to the ICU. However, the rate of RRT is lower in patients with COVID-19 or ACE2-associated viruses when compared with patients infected with non-ACE2-binding viruses, which might partly be due to the lower frequencies of shock and use of vasopressors in these two virus groups. Prospective studies are necessary to demonstrate whether modulation of the ACE2 axis with Renin-Angiotensin System inhibitors impacts the rates of AKI and whether they are beneficial or harmful in COVID-19 patients.

MISE EN CONTEXTE: L'insuffisance rénale aiguë (IRA) est une complication potentiellement mortelle de la maladie à coronavirus-2019 (COVID-19). Obligatoire du Coronavirus 2 du Syndrome Respiratoire Aigu Sévère (SARS-CoV-2), le virus responsable du COVID-19, à son récepteur, l'enzyme de conversion de l'angiotensine 2 (ACE2), entraîne une entrée virale et peut provoquer une IRA. OBJECTIFS DE L'ÉTUDE: Nous avons effectué une revue systématique et une méta-analyse des fréquences de l'IRA et de la thérapie de remplacement renal (RRT) chez les patients COVID-19 gravement malades et a comparé ces fréquences avec les patients qui ont été infectés par des voies respiratoires virus qui lient ou régulent négativement l'ACE2 (virus associés à l'ACE2) et les virus qui ne régulent pas négativement ni ne lient l'ACE2 (virus non associés à l'ACE2). CADRE ET TYPE D'ÉTUDE: Revue systématique et méta-analyse. Des études d'observation sur le COVID-19 et d'autres infections virales respiratoires signalant une AKI et une RRT ont été incluses. Les critères d'exclusion étaient des articles non anglophones, des articles non évalués par des pairs, des articles de revue, des études incluant des patients moins de 18 ans, les études incluant moins de 10 patients et les études ne rapportant pas les taux d'IRA et de RRT. PATIENTS: Adultes COVID-19, syndrome respiratoire aigu sévère (SRAS), syndrome respiratoire du Moyen-Orient (MERS) et malades de la grippe. MESURES: Nous avons extrait les données suivantes des études incluses : auteur, année, lieu de l'étude, âge, sexe, race, diabète sucré, hypertension, maladie rénale chronique, état de choc, utilisation de vasopresseurs, mortalité, admission en unité de soins intensifs (USI), Mortalité en soins intensifs, AKI et RRT. MÉTHODOLOGIE: Nous avons systématiquement recherché dans PubMed et EMBASE les articles rapportant AKI ou RRT. AKI a été défini par les auteurs des études incluses. La maladie grave a été définie par l'admission aux soins intensifs. Nous avons effectué une méta-analyse à effets aléatoires pour calculer estimations regroupées pour le taux d'IRA et de RRT au sein de chaque groupe de virus à l'aide d'un modèle de régression logistique d'interception aléatoire. RÉSULTATS: Sur 23 655 patients hospitalisés et gravement malades COVID-19, les fréquences AKI n'étaient pas significativement différentes entre patients COVID-19 (51 %, intervalle de confiance à 95 % [IC] : 44 %-57 %) et patients gravement malades infectés par l'ACE2 associé (56 %, IC à 95 % : 37 % à 74 %, P = 0,610) ou des virus non associés à l'ACE2 (63 %, IC à 95 % : 43 % à 79 %, P = 0,255). Tarifs RRT groupés n'étaient pas non plus significativement différents entre les patients hospitalisés gravement malades atteints de COVID-19 (20 %, IC à 95 % : 16 % à 24 %) et virus associés à l'ACE2 (18 %, IC à 95 % : 8 % à 33 %, P = 0,747). Taux de RRT pour les virus associés au COVID-19 et à l'ACE2 étaient significativement différents (P < 0,001 pour les deux) des virus non associés à l'ACE2 (49 %, IC à 95 % : 44 % à 54 %). Après ajustement pour le choc ou l'utilisation de vasopresseurs, les taux d'IRA et de RRT n'étaient pas significativement différents entre les groupes. LIMITES DE L'ÉTUDE: Les limites de cette étude incluent l'hétérogénéité des définitions de l'IRA qui ont été utilisées pour différents virus études. Nous n'avons pas pu faire correspondre la gravité de l'infection ou faire une correspondance de propension entre les études. La plupart des études incluses ont été menées de manière rétrospective. Enfin, nous n'avons pas inclus les publications non anglophones. CONCLUSIONS: Nos résultats suggèrent que l'association virale ACE2 ne modifie pas de manière significative les taux d'IRA et de RRT parmi les patients gravement malades admis aux soins intensifs. Cependant, le taux de RRT est plus faible chez les patients atteints de COVID-19 ou associés à l'ACE2 virus par rapport aux patients infectés par des virus ne se liant pas à l'ACE2, ce qui pourrait être dû en partie à la plus faible fréquences de choc et utilisation de vasopresseurs dans ces deux groupes de virus. Des études prospectives sont nécessaires pour démontrer si la modulation de l'axe ACE2 avec les inhibiteurs du système rénine-angiotensine a un impact sur les taux d'IRA et si ells sont bénéfiques ou nocifs chez les patients COVID-19.

Pregnancy and COVID-19: pharmacologic considerations.

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.