CROI 2022: Other COVID-19 studies
CROI 2022 included 214 studies that related to COVID-19 – almost 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 also cover a wide range of topics, though some have small sample sizes or are retrospective in nature.
Further research is still needed to develop strategies to mitigate and eliminate COVID-19.
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. 
Household contacts of positive COVID-19 index cases were recruited and randomised to CAS+IMD (n=841) or placebo (n=842).
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.
These data were collected before the emergence of the Omicron variant and further data are required to assess efficacy against this, and future, variants.
A retrospective study evaluated severity of COVID-19 in HIV positive people on effective ART with undetectable viral load. 
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).
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. This limited benefit might only be in adults > 50 years old.
It should be noted that this is a retrospective study and randomised controlled trials are required.
Finally, a phase three placebo-controlled study evaluated the impact of a 3-day remdesivir regimen upon COVID-19 progression. 
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.
However, several earlier studies have reported no benefit from remdesivir on risk or mortality remdesivir in moderate and severe stage infection. [4, 5]
A study of COVID-19 cases in Qatar reported a 50% reduction of transmissibility following vaccination. 
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.
CT values from PCR tests conducted between February 2020 to July 2021 were analysed.
Four groups were identified:
- COVID positive and unvaccinated (n=301,424).
- Re-infection and unvaccinated (n=1,695)
- Breakthrough COVID-19 after Pfizer vaccine (n=4,262).
- Breakthrough COVID-19 after Moderna vaccine (n=283).
Average CT values increased for breakthrough cases: Pfizer (1.3 cycles higher; 95%: CI: 0.9 to 1.8) < Moderna (3.2, 95% CI: 1.9 to 4.5) < unvaccinated (4.0, 95% CI: 3.5 to 4.5).
Blood clots are a known complication of COVID-19 and have been associated, in rare cases, with COVID-19 vaccinations. 
Dr Mauricio Montano from the Gladstone Institute of Virology presented results from a mechanistic study investigating the composition and properties of these clots. 
Clots in COVID-19 disease are abnormal and more resistant to anticoagulation with standard therapy.
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.
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.
This study provides important insights into COVID-19 coagulopathy and highlights a potential therapeutic target.
COVID-19 linked to higher rate of false positive HIV tests
Inflammation and infectious diseases have been associated with false positive (FP) HIV tests.
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). 
Overall, 10.2% (n=2,382) were COVID-19 positive and >99% of all HIV tests were negative.
True positive and FP tests were reported for 167 and 70 people, respectively.
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).
This study only evaluated FP using the Elecsys HIV Duo 4th generation test (Roche).
Management of severe COVID-19: tocilizimab, biosimilars, and increased dosing
Tocilizumab is a humanised monoclonal antibody against the IL-6 receptor. It is recommended for people with COVID-19 that have CRP >7.5 mg/dL and works by reducing the impact of the inflammation from the COVID-19 cytokine storm.
A multicentre double-blind active-controlled trial was conducted in India to evaluate whether biosimilar tocilizumab reduces the requirement for mechanical ventilation. 
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.
An observational cohort study confirmed that administration of tocilizumab in people with severe COVID-19 is only beneficial for those with CRP ≥7.5mg/dL. 
Just under 1000 people with severe COVID-19 pneumonia were randomised 2:1 to monotherapy (n=597) or intensification with tocilizumab (n=395).
The primary endpoint was mortality at day 28. Intensification with tocilizumab reduced survival benefit in participants with CRP <7.5 mg/dL.
Substantial benefit from intensification was conferred for participants with CRP >15 mg/dL.
However, larger studies are required to determine clinical cut-offs for intensification with tocilizumab.
Zinc has important roles in immune cell function, antioxidant and anti-inflammatory activity.
A mechanistic study evaluated serum zinc levels in people at time of COVID-19 diagnosis (n=159). 
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%).
Participants with zinc deficiency (serum zinc < 75 µg/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..
Despite a large proportion of presentations on COVID-19, there were relatively few significant findings reported.
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.
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.
Studies on long COVID (PASC) at the conference have also been reported in an earlier issue of HTB. 
Unless stated otherwise, references are to the 29th Conference on Retroviruses and Opportunistic Infections, 12–16 and 22–24 February 2022, virtual meeting.
- O’Brien M et al. Casirivimab and imdevimab combination provides long-term protection against COVID-19. CROI 2022. 12-16 February, virtual. Oral abstract 104.
- 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.
- Webb B et al. Safety of remdesivir vs placebo in nonhospitalized patients with COVID-19. CROI 2022. 12-16 February, virtual. Poster abstract 456.
- No survival benefit from remdesivir, hydroxychloroquine, lopinavir/r or interferon-β1a in moderate and severe COVID-19: interim results from the WHO SOLIDARITY study. HTB (November 2020).
- Major review finds little benefit of remdesivir in people hospitalised with COVID-19. HTB (March 2022).
- Abu-Raddad L et al. Infectiousness of breakthrough infections after vaccination and natural infection. CROI 2022. 12-16 February, virtual. Oral abstract 49.
- 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).
- Montano M et al. SARS-COV-2 spike binds fibrinogen-inducing abnormal inflammatory blood clots. CROI 2022. 12-16 February, virtual. Oral abstract 26.
- 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.
- Kumarasamy N et al. Tocilizumab (biosimilar) use in cytokine storm of severe COVID-19 pneumonia. CROI 2022. 12-16 February, virtual. Poster abstract 636.
- 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.
- Mouchati CF et al. Zinc deficiency is independently associated with increased COVID-19 disease severity. CROI 2022. 12-16 February, virtual. Poster abstract 643.
- i-Base. COVID-19: long COVID
This report was first published on 30 April 2022.