{"id":42776,"date":"2022-05-02T07:42:09","date_gmt":"2022-05-02T07:42:09","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=42776"},"modified":"2022-05-04T15:12:28","modified_gmt":"2022-05-04T15:12:28","slug":"croi-2022-other-covid-19-studies","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/42776","title":{"rendered":"CROI 2022: Other COVID-19 studies"},"content":{"rendered":"<div><\/div>\n<div>\n<p class=\"HTBsubhead3authorcredit\"><strong><span lang=\"EN-US\">Kirk Taylor, HIV i-Base<\/span><\/strong><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYbold\"><strong><span lang=\"EN-US\"><img loading=\"lazy\" decoding=\"async\" class=\" alignright\" src=\"https:\/\/i-base.info\/wp-content\/uploads\/2020\/03\/COVID-19-graphic.png\" width=\"231\" height=\"142\" \/>CROI 2022 included 214 studies that related to COVID-19 \u2013\u00a0almost a quarter of the overall programme. <\/span><\/strong><\/p>\n<p class=\"HTBBODYbold\"><span lang=\"EN-US\">These covered all aspect of the new pandemic, including antivirals, transmission, testing and disease management. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYbold\"><span lang=\"EN-US\">The selected studies reported below also cover a wide range of topics, though <\/span><span lang=\"EN-US\">some have small sample sizes or are retrospective in nature.<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYbold\"><span lang=\"EN-US\">Further research is still needed to develop strategies to mitigate and eliminate COVID-19.<\/span><\/p>\n<h2>COVID antivirals<\/h2>\n<\/div>\n<div>Several studies reported data on antivirals for people with COVID-19. We start with\u00a0three studies covering COVID-19 pre-exposure prophylaxis, disease severity for people with HIV on effective ART and use of remdesivir in non-hospitalised people. [1, 2, 3]<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A double-blind phase 3 study reported efficacy and safety data of sub-cutaneous (SC) casirivimab plus imdevimab (CAS+IMD; 1200 mg SC) as COVID-19 pre-exposure prophylaxis. [1] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Household contacts of positive COVID-19 index cases were recruited and randomised to CAS+IMD (n=841) or placebo (n=842). <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Primary efficacy at day 28 showed an 81.4% reduction in symptomatic COVID-19 cases and 66.4% reduction in transmission to household contacts. Efficacy was maintained at similar levels at month 7. No new safety concerns were reported. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">These data were collected before the emergence of the Omicron variant and further data are required to assess efficacy against this, and future, variants.\u00a0\u00a0\u00a0 <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A retrospective study evaluated severity of COVID-19 in HIV positive people on effective ART with undetectable viral load. [2]<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Participants were recruited from 69 Spanish clinics and were female (21%) and median age was 50 (IQR: 39 to 58). COVID-19 severity was assessed in groups stratified by ART regimen as follows TDF\/FTC (n=6,160), TAF\/FTC (n=20,432), ABC\/3TC (n=13,715) and other (n=11,251). <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The relative risk of COVID-19 was similar for each group. However, a modest reduction in COVID-19 severity was reported for HIV positive people on TDF\/FTC regimens. \u00a0This limited benefit might only be in adults &gt; 50 years old.<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">It should be noted that this is a retrospective study and randomised controlled trials are required.\u00a0\u00a0 <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Finally, a phase three placebo-controlled study evaluated the impact of a 3-day remdesivir regimen upon COVID-19 progression. [3] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Participants were recruited from USA, UK, Spain and Denmark and randomised to remdesivir (n=279) or placebo (n=283). Remdesivir reduced hospitalisation of people at high risk of COVID-19. No serious adverse events were recorded in either group and remdesivir was well-tolerated in non-hospitalised individuals.<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">However, several earlier studies have reported no benefit from remdesivir on risk or mortality \u00a0remdesivir in moderate and severe stage infection. [4, 5]<\/span><\/p>\n<h2>Transmissibility<\/h2>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A study of COVID-19 cases in Qatar reported a 50% reduction of transmissibility following vaccination. [6] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Cycle thresholds (CT) of RT-PCR COVID-19 tests indicate the level of virus in a sample. The authors used CT as a surrogate marker for transmissibility with higher CT values indicating lower viral load and reduced transmissibility. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">CT values from PCR tests conducted between February 2020 to July 2021 were analysed. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Four groups were identified: <\/span><\/p>\n<\/div>\n<div>\n<ul>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">COVID positive and unvaccinated (n=301,424).<\/span><\/li>\n<li class=\"HTBBODYindent\">Re-infection and unvaccinated (n=1,695)<\/li>\n<li class=\"HTBBODYindent\">Breakthrough COVID-19 after Pfizer vaccine (n=4,262).<\/li>\n<li class=\"HTBBODYindent\">Breakthrough COVID-19 after Moderna vaccine (n=283).<\/li>\n<\/ul>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Average CT values increased for breakthrough cases: Pfizer (1.3 cycles higher; 95%: CI: 0.9 to 1.8) &lt; Moderna (3.2, 95% CI: 1.9 to 4.5) &lt; unvaccinated (4.0, 95% CI: 3.5 to 4.5).<\/span><\/p>\n<\/div>\n<div>\n<h2>COVID-19 coagulopathy<\/h2>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Blood clots are a known complication of COVID-19 and have been associated, in rare cases, with COVID-19 vaccinations. [7] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Dr Mauricio Montano from the Gladstone Institute of Virology presented results from a mechanistic study investigating the composition and properties of these clots. [8] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Clots in COVID-19 disease are abnormal and more resistant to anticoagulation with standard therapy. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Lab studies demonstrated that spike protein increased fibrin polymerisation, leading to more complex and dense clots. Spike protein interacted with multiple sites on fibrinogen, including a site important for driving inflammatory responses. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A mouse model confirmed enhanced coagulopathy induced by spike protein. Infusion of 5B8 antibodies against the inflammatory epitope of fibrinogen reduced fibrinogen deposits and inflammatory responses without altering haemostasis. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">This study provides important insights into COVID-19 coagulopathy and highlights a potential therapeutic target.<\/span><\/p>\n<h2>COVID-19 linked to higher rate of false positive HIV tests<\/h2>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\">Inflammation and infectious diseases have been associated with false positive (FP) HIV tests.<\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A retrospective cross-sectional study in Detroit evaluated COVID-19 positivity within two weeks of a positive HIV test using medical records (n=23,278). [9] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Overall, 10.2% (n=2,382) were COVID-19 positive and &gt;99% of all HIV tests were negative. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">True positive and FP tests were reported for 167 and 70 people, respectively. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">FP accounted for 0.3% of results, but were more common for COVID-19 positive individuals, with an odds ratio of 7.04 (p=0.001). <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">This study only evaluated FP using the Elecsys HIV Duo 4th generation test (Roche).<\/span><\/p>\n<\/div>\n<div>\n<h2 class=\"HTBBODYtext\">Management of severe COVID-19: tocilizimab, biosimilars, and increased dosing<\/h2>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Tocilizumab is a humanised monoclonal antibody against the IL-6 receptor. It is recommended for people with COVID-19 that have CRP &gt;7.5 mg\/dL and works by reducing the impact of the inflammation from the COVID-19 cytokine storm. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A multicentre double-blind active-controlled trial was conducted in India to evaluate whether biosimilar tocilizumab reduces the requirement for mechanical ventilation. [10] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The study randomised 172 participants with severe COVID-19 in a 3:1 ratio to either biosimilar (n=131) or reference product (n=41). Biosimilar product performance was comparable to reference product. The results show that biosimilars might provide a more cost-effective alternative for management of severe COVID-19 in resource-limited settings. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">An observational cohort study confirmed that administration of tocilizumab in people with severe COVID-19 is only beneficial for those with CRP \u22657.5mg\/dL. [11]<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Just under 1000 people with severe COVID-19 pneumonia were randomised 2:1 to monotherapy (n=597) or intensification with tocilizumab (n=395). <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The primary endpoint was mortality at day 28. Intensification with tocilizumab reduced survival benefit in participants with CRP &lt;7.5 mg\/dL. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Substantial benefit from intensification was conferred for participants with CRP &gt;15 mg\/dL. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">However, larger studies are required to determine clinical cut-offs for intensification with tocilizumab.<\/span><\/p>\n<h2>Zinc supplementation<\/h2>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Zinc has important roles in immune cell function, antioxidant and anti-inflammatory activity. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">A mechanistic study evaluated serum zinc levels in people at time of COVID-19 diagnosis (n=159). [12] <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Median age was 53 (IQR: 38 to 63), 42% were female and 48% were white. COVID-19 was classified as asymptomatic or mild (50%), moderate (41.5%) or severe (8.5%). <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Participants with zinc deficiency (serum zinc &lt; 75 \u00b5g\/dL) had significantly increased COVID-19 severity (AHR 0.24; 95% CI: 0.06 to 0.93, p=0.037), although the confidence intervals were wide..<\/span><\/p>\n<\/div>\n<div>\n<h3 class=\"HTBcommenttitle\">comment<\/h3>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><b>Despite a large proportion of presentations on COVID-19, there were relatively few significant findings reported. <\/b><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><b>As countries shift public health focus from pandemic to endemic strategies, it will be important to continue research into the efficacy of antiviral therapies and vaccines. <\/b><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><b>Although potential strategies for prophylactic COVID-19 antivirals were reported, case numbers remain globally high and the lag time between exposure and onset of symptoms may limit the usefulness of such strategies.\u00a0<\/b><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><b>Studies on long COVID (PASC) at the conference have also been reported in an earlier issue of HTB. [13]<\/b><\/p>\n<\/div>\n<div>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">References<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">Unless stated otherwise, references are to the 29th Conference on Retroviruses and Opportunistic Infections, 12\u201316 and 22\u201324 February 2022, virtual meeting.\u00a0<\/span><\/p>\n<\/div>\n<div>\n<ol>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">O\u2019Brien M et al. Casirivimab and imdevimab combination provides long-term protection against COVID-19. CROI 2022. 12-16 February, virtual. Oral abstract 104.<br \/>\n<\/span><span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/casirivimab-and-imdevimab-combination-provides-long-term-protection-against-covid-19\/\">https:\/\/www.croiconference.org\/abstract\/casirivimab-and-imdevimab-combination-provides-long-term-protection-against-covid-19\/<\/a><\/span><span lang=\"EN-US\">\u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Del Amo J et al. Tenofovir disoproxil fumarate and severity of COVID-19 in people with HIV infection. CROI 2022. 12-16 February, virtual. Poster abstract 867.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/tenofovir-disoproxil-fumarate-and-severity-of-covid-19-in-people-with-hiv-infection\/\">https:\/\/www.croiconference.org\/abstract\/tenofovir-disoproxil-fumarate-and-severity-of-covid-19-in-people-with-hiv-infection\/<\/a><\/li>\n<li class=\"HTBreferences\">Webb B et al. Safety of remdesivir vs placebo in nonhospitalized patients with COVID-19. CROI 2022. 12-16 February, virtual. Poster abstract 456.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/safety-of-remdesivir-vs-placebo-in-nonhospitalized-patients-with-covid-19\/\">https:\/\/www.croiconference.org\/abstract\/safety-of-remdesivir-vs-placebo-in-nonhospitalized-patients-with-covid-19\/<\/a><\/span><span lang=\"EN-US\">\u00a0\u00a0<\/span><\/li>\n<li class=\"HTBreferences\">No survival benefit from remdesivir, hydroxychloroquine, lopinavir\/r or interferon-\u03b21a in moderate and severe COVID-19: interim results from the WHO SOLIDARITY study. HTB (November 2020).<br \/>\nhttps:\/\/i-base.info\/htb\/39223<\/li>\n<li class=\"HTBreferences\">Major review finds little benefit of remdesivir in people hospitalised with COVID-19. HTB (March 2022).<br \/>\nhttps:\/\/i-base.info\/htb\/42376<\/li>\n<li class=\"HTBreferences\">Abu-Raddad L et al. Infectiousness of breakthrough infections after vaccination and natural infection. CROI 2022. 12-16 February, virtual. Oral abstract 49.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/infectiousness-of-breakthrough-infections-after-vaccination-and-natural-infection\/\">https:\/\/www.croiconference.org\/abstract\/infectiousness-of-breakthrough-infections-after-vaccination-and-natural-infection\/<\/a><\/span><span lang=\"EN-US\">\u00a0 \u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Greinacher A et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. NEJM vol 384 issue 22 (2092-2101). DOI: 10.1056\/NEJMoa2104840. (3 June 2021).<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2104840\">https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2104840<\/a><\/span><span lang=\"EN-US\">\u00a0\u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Montano M et al. SARS-COV-2 spike binds fibrinogen-inducing abnormal inflammatory blood clots. CROI 2022. 12-16 February, virtual. Oral abstract 26.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/sars-cov-2-spike-binds-fibrinogen-inducing-abnormal-inflammatory-blood-clots\/\">https:\/\/www.croiconference.org\/abstract\/sars-cov-2-spike-binds-fibrinogen-inducing-abnormal-inflammatory-blood-clots\/<\/a><\/span><\/li>\n<li class=\"HTBreferences\">Shallal A et al. Increase in false positive 4th generation HIV tests in patients with COVID-19 disease. CROI 2022. 12-16 February, virtual. Oral abstract 26.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/increase-in-false-positive-4th-generation-hiv-tests-in-patients-with-covid-19-disease\/\">https:\/\/www.croiconference.org\/abstract\/increase-in-false-positive-4th-generation-hiv-tests-in-patients-with-covid-19-disease\/<\/a><\/span><span lang=\"EN-US\">\u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Kumarasamy N et al. Tocilizumab (biosimilar) use in cytokine storm of severe COVID-19 pneumonia. CROI 2022. 12-16 February, virtual. Poster abstract 636.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/tocilizumab-biosimilar-use-in-cytokine-storm-of-severe-covid-19-pneumonia\/\">https:\/\/www.croiconference.org\/abstract\/tocilizumab-biosimilar-use-in-cytokine-storm-of-severe-covid-19-pneumonia\/<\/a><\/span><span lang=\"EN-US\">\u00a0 \u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Mussini C et al. Do all critically ill COVID-19 patients benefit from intensifying with tocilizumab? CROI 2022. 12-16 February, virtual. Poster abstract 465.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/do-all-critically-ill-covid-19-patients-benefit-from-intensifying-with-tocilizumab\/\">https:\/\/www.croiconference.org\/abstract\/do-all-critically-ill-covid-19-patients-benefit-from-intensifying-with-tocilizumab\/<\/a><\/span><span lang=\"EN-US\">\u00a0\u00a0<\/span><\/li>\n<li class=\"HTBreferences\">Mouchati CF et al. Zinc deficiency is independently associated with increased COVID-19 disease severity. CROI 2022. 12-16 February, virtual. Poster abstract 643.<br \/>\n<span lang=\"EN-US\"><a href=\"https:\/\/www.croiconference.org\/abstract\/zinc-deficiency-is-independently-associated-with-increased-covid-19-disease-severity\/\">https:\/\/www.croiconference.org\/abstract\/zinc-deficiency-is-independently-associated-with-increased-covid-19-disease-severity\/<\/a><\/span><\/li>\n<li class=\"HTBreferences\">i-Base. COVID-19: long COVID<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/section\/long-covid\">https:\/\/i-base.info\/htb\/section\/long-covid<\/a><\/li>\n<\/ol>\n<p><em>This report was first published on 30 April 2022.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Kirk Taylor, HIV i-Base CROI 2022 included 214 studies that related to COVID-19 \u2013\u00a0almost a quarter of the overall programme. These covered all aspect of the new pandemic, including antivirals, transmission, testing and disease management. The selected studies reported below &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,31,278],"tags":[],"class_list":["post-42776","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-opportunistic-infections-coinfections-and-complications","category-covid-19"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42776","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=42776"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42776\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=42776"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=42776"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=42776"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}