Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.

OBJECTIVE: To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics. METHODS: We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality. RESULTS: During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex. CONCLUSION: No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.

BACKGROUND: Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure. METHODS: A retrospective population based open cohort study using the UK primary care database, 'The Health Improvement Network,' between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health. RESULTS: The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71-2.48), chronic fatigue syndrome (1.47; 1.08-2.00), chronic lower back pain (1.99; 1.68-2.35), restless leg syndrome (1.82; 1.41-2.35) and irritable bowel syndrome (1.15; 1.08-1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88-1.13), chronic headache (1.04; 0.59-1.86), interstitial cystitis (1.19; 0.51-2.74), vulvodynia (0.65; 0.34-1.26), chronic prostatitis (0.34; 0.07-1.77) and myofascial pain syndrome (0.88; 0.36-2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS. INTERPRETATION: The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.