Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants

Oskotsky T, Maric I, Tang A, Oskotsky B, Wong RJ, Aghaeepour N, Sirota M, Stevenson DK. JAMA Netw Open. 2021 Nov 1;4(11):e2133090. [CrossRef] [PubMed]

Importance: Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)—specifically fluoxetine hydrochloride and fluvoxamine maleate—with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.

Objective: The authors investigated the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).

Design, setting, and participants: This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US. A total of 3401 adult patients with COVID-19 prescribed SSRIs were identified. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).

Conclusions and Relevance:  These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

Lopez Bernal J, Andrews N, Gower C, et al. N Engl J Med. 2021 Jul 21. [CrossRef] [PubMed] [Epub ahead of print.] 

The Pfizer-BioNTech and AstraZeneca vaccines — the primary vaccine options in the United Kingdom — were less effective against symptomatic COVID-19 when people were exposed to the Delta variant of SARS-CoV-2 compared with the Alpha variant (known as B.1.1.7, or the UK variant), according to a study published online today in the New England Journal of Medicine. The Indian investigators used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations.

Azithromycin for Community Treatment of Suspected COVID-19 in People at Increased Risk of an Adverse Clinical Course in the UK (PRINCIPLE): A Randomised, Controlled, Open-Label, Adaptive Platform Trial

PRINCIPLE Trial Collaborative Group. Lancet. 2021 Mar 4:S0140-6736(21)00461-X. [CrossRef] [PubMed]

Azithromycin, an antibiotic with anti-inflammatory and potential antiviral properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.

In this UK-based, primary care, open-label, multi-arm, adaptive platform randomized trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomization: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analyzed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis.

Participants were enrolled between May 22 and Nov 30, 2020. 2265 participants were randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azithromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.

These findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalization for people with suspected COVID-19 in the community.

The Lancet Commission on Public Policy and Health in the Trump Era

Himmelstein DU, Woolhandler S, Cooney R, McKee M, Horton R.. Lancet. 2018 Sep 22;392(10152):993-995. [CrossRef] [PubMed]

The article is lengthy at 49 pages and has no abstract available. The executive summary runs about 2 pages. The key messages listed in the article are below. Links to the executive summary and the whole article are at the end of this summary.

Key messages

• Politicised and repudiated science, leaving the USA unprepared and exposed to the COVID-19 pandemic
• Eviscerated environmental regulation, hastening global warming
• Incited racial, nativist, and religious hatred, provoking vigilante and police violence
• Denied refuge to migrants fleeing violence and oppression, and abused immigrant detainees
• Undermined health coverage
• Weakened food assistance programmes
• Curtailed reproductive rights
• Undermined global cooperation for health, and triggered trade wars
• Shifted resources from social programmes to military spending and tax windfalls for corporations and the wealthy
• Subverted democracy both nationally and internationally
• Although the Trump administration policies posed a uniquely urgent threat to health,
• damaging neoliberal policies predated and abetted his ascendance:
• Life expectancy in the USA has lagged behind other wealthy nations since 1980 and
• began falling in 2014
• The chronically high mortality of Native Americans started rising in 1999, while
• yawning disparities between Black and white people persisted and progress on racial
• equity in other domains (eg, education, housing, income and policing) halted or
• reversed
• Substance abuse deaths greatly increased
• Income and wealth inequality widened
• Incarceration increased four-fold, initiated by President Nixon’s racially motivated war
• on drugs and compounded by harsh laws enacted under Presidents Reagan and Clinton
• Welfare eligibility restrictions implemented by President Clinton removed benefits from millions
• Deindustrialisation spurred by trade agreements that favoured corporate interests
• over labour protections reduced economic opportunity in many regions of the USA,
• damaging health and increasing receptivity to racist and xenophobic appeals
• Market-based reforms commercialised and bureaucratised medical care, raised costs, and shifted care toward high-income US residents
• Despite the Affordable Care Act, nearly 30 million people in the USA remained
• uninsured and many more were covered but still unable to afford care
• Funding cuts reduced the front-line public health workforce by 20%
• The Biden administration must cancel Trump’s actions and also address the healthdamaging structural problems that were present before Trump’s presidency:
• Raise taxes on high-income people and use the proceeds to bolster social, educational, and health programmes, and address urgent environmental problems
• Mobilise against the structural racism and police violence that shorten the lives of
• people of colour
• Replace means-tested programmes such as Medicaid that segregate low-income
• people, with unified programmes such as national health insurance that serve all
• US residents, aligning the interests of the middle class and the poor in maintaining excellence
• Reclaim the US Government’s role in delivering health and social services, and stop channelling public funds through private firms whose profit-seeking skews priorities
• Redirect public investments from militarism, corporate subsidies, and distorted
• medical priorities to domestic and global fairness, environmental protection,
• and neglected public health and social interventions
• Reinvigorate US democracy by reforming campaign financing, reinforcing voting,
• immigration, and labour rights, and restoring oversight of presidential prerogatives

Full Text and Executive Summary

The Lancet Commission on Public Policy and Health in the Trump Era

Himmelstein DU, Woolhandler S, Cooney R, McKee M, Horton R. Lancet. 2018 Sep 22;392(10152):993-995. [CrossRef] [PubMed]

The article is lengthy at 49 pages and has not abstract available. The executive summary runs about 2 pages. The key messages listed in the article are below. Links to the executive summary and the whole article are at the end the key messages.

Key messages

• Politicised and repudiated science, leaving the USA unprepared and exposed to the COVID-19 pandemic
• Eviscerated environmental regulation, hastening global warming
• Incited racial, nativist, and religious hatred, provoking vigilante and police violence
• Denied refuge to migrants fleeing violence and oppression, and abused immigrant detainees
• Undermined health coverage
• Weakened food assistance programmes
• Curtailed reproductive rights
• Undermined global cooperation for health, and triggered trade wars
• Shifted resources from social programmes to military spending and tax windfalls for corporations and the wealthy
• Subverted democracy both nationally and internationally
• Although the Trump administration policies posed a uniquely urgent threat to health,
• damaging neoliberal policies predated and abetted his ascendance:
• Life expectancy in the USA has lagged behind other wealthy nations since 1980 and
• began falling in 2014
• The chronically high mortality of Native Americans started rising in 1999, while
• yawning disparities between Black and white people persisted and progress on racial
• equity in other domains (eg, education, housing, income and policing) halted or
• reversed
• Substance abuse deaths greatly increased
• Income and wealth inequality widened
• Incarceration increased four-fold, initiated by President Nixon’s racially motivated war
• on drugs and compounded by harsh laws enacted under Presidents Reagan and Clinton
• Welfare eligibility restrictions implemented by President Clinton removed benefits from millions
• Deindustrialisation spurred by trade agreements that favoured corporate interests
• over labour protections reduced economic opportunity in many regions of the USA,
• damaging health and increasing receptivity to racist and xenophobic appeals
• Market-based reforms commercialised and bureaucratised medical care, raised costs, and shifted care toward high-income US residents
• Despite the Affordable Care Act, nearly 30 million people in the USA remained
• uninsured and many more were covered but still unable to afford care
• Funding cuts reduced the front-line public health workforce by 20%
• The Biden administration must cancel Trump’s actions and also address the healthdamaging structural problems that were present before Trump’s presidency:
• Raise taxes on high-income people and use the proceeds to bolster social, educational, and health programmes, and address urgent environmental problems
• Mobilise against the structural racism and police violence that shorten the lives of
• people of colour
• Replace means-tested programmes such as Medicaid that segregate low-income
• people, with unified programmes such as national health insurance that serve all
• US residents, aligning the interests of the middle class and the poor in maintaining excellence
• Reclaim the US Government’s role in delivering health and social services, and stop channelling public funds through private firms whose profit-seeking skews priorities
• Redirect public investments from militarism, corporate subsidies, and distorted
• medical priorities to domestic and global fairness, environmental protection,
• and neglected public health and social interventions
• Reinvigorate US democracy by reforming campaign financing, reinforcing voting,
• immigration, and labour rights, and restoring oversight of presidential prerogatives

Full Text and Executive Summary