Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Risk if ART is deferred is taken from [328]. The predicted 6-month risk if ART is initiated is based on the assumption that the rate with immediate therapy initiation is one-third the rate without therapy initiation. This (probably conservative) value is based on considering evidence from multiple sources, including references [32,[329][330][331][332][333].BHIVA treatment guidelines 569 r 2008 British HIV Association HIV Medicine (2008) 9, 563-608 but high CD4 percentages, but also may support a decision to start therapy earlier in patients with absolute CD4 counts 4350 cells/mL but with low CD4 percentages {e.g. o14%, where Pneumocystis carinii pneumonia (PCP) prophylaxis is indicated [35]; some studies have indicated increased risk of disease progression in patients with CD4 percentages o15-17% [36]}. Patients with a CD4 count 4350 cells/mLAs detailed above, at CD4 counts 4350 cells/mL, multiple cohort studies have suggested that there might be benefits to ART. This is supported by data from the substudy of patients not on therapy at entry to the SMART study [32]. Some of the previous concerns about earlier initiation of therapy have been reduced because of the availability of simpler, less toxic and better tolerated antiretroviral regimens, improved pharmacokinetic profiles and increasing options after virological failure. For the majority of patients, the absolute risk of deferring therapy until the CD4 count is o350 cells/mL is likely to be low, but in a subgroup at particularly high risk of clinical events that may be preventable by ART, this is not the case. For all these reasons, in a small number of patients, treatment may be started or considered before the CD4 count is below 350 cells/mL, including the following: AIDS diagnosis (e.g. Kaposi's sarcoma); any HIV-related comorbidity; hepatitis B infection, where treatment of hepatitis B is indicated (see hepatitis guidelines); hepatitis C infection in some cases, where treatment for hepatitis is deferred; low CD4 percentage (e.g. o14%, where PCP prophylaxis would be indicated); established CVD or a very high risk of cardiovascular events (e.g. Framingham risk of CVD 420% over 10 years).Additionally, it is likely that successful antiretroviral treatment, by reducing viral load, reduces infectivity irrespective of the current CD4 cell count, and this may be taken into account in deciding on the timing of starting treatment, particularly in discordant couples where the infected partner has a high viral load. This is likely to be an issue in a very small number of patients, and it must be stressed that antiretroviral treatment in this context would be an adjunct rather than an alternative to safer sex.In patients who do not have an AIDS diagnosis or coinfection with hepatitis B or C virus, and whose CD4 counts are above 500 cells/mL, the benefits of starting therapy remain unclear, the risk of deferring therapy is low, and we recommend that they consider enrolment in the START study, where this is an option. ComorbiditiesWhilst it has been clearly shown that...

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

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Table of Contents 1. Levels of evidence1.1 Reference2. Introduction3. Auditable targets4. Table summaries4.1 Initial diagnosis4.2 Assessment of ART‐naïve individuals4.3 ART initiation4.4 Initial assessment following commencement of ART4.5 Routine monitoring on ART4.6 References5. Newly diagnosed and transferring HIV‐positive individuals5.1 Initial HIV‐1 diagnosis5.2 Tests to determine whether acquisition of HIV infection is recent5.3 Individuals transferring care from a different HIV healthcare setting5.4 Communication with general practitioners and shared care5.5 Recommendations5.6 References6. Patient history6.1 Initial HIV‐1 diagnosis6.2 Monitoring of ART‐naïve patients6.3 Pre‐ART initiation assessment6.4 Monitoring individuals established on ART6.5 Assessment of adherence6.6 Recommendations6.7 References7. Examination7.1 Recommendations8. Identifying the need for psychological support8.1 References9. Assessment of immune status9.1 CD4 T cell counts9.2 CD4 T cell percentage9.3 References10. HIV viral load10.1 Initial diagnosis/ART naïve10.2 Post ART initiation10.3 Individuals established on ART10.4 Recommendations10.5 References11. Technical aspects of viral load testing11.1 References12. Viral load kinetics during ART and viral load ‘blips’12.1 References13. Proviral DNA load13.1 References14. Resistance testing14.1 Initial HIV‐1 diagnosis14.2 ART‐naïve14.3 Post treatment initiation14.4 ART‐experienced14.5 References15. Subtype determination15.1 Disease progression15.2 Transmission15.3 Performance of molecular diagnostic assays15.4 Response to therapy15.5 Development of drug resistance15.6 References16. Other tests to guide use of specific antiretroviral agents16.1 Tropism testing16.2 HLA B*5701 testing16.3 References17. Therapeutic drug monitoring17.1 Recommendations17.2 References18. Biochemistry testing18.1 Introduction18.2 Liver function18.3 Renal function18.4 Dyslipidaemia in HIV‐infected individuals18.5 Other biomarkers18.6 Bone disease in HIV‐infected patients18.7 References19. Haematology19.1 Haematological assessment and monitoring19.2 Recommendations19.3 References20. Serology20.1 Overview20.2 Hepatitis viruses20.3 Herpes viruses20.4 Measles and rubella20.5 Cytomegalovirus (CMV)20.6 References21. Other microbiological screening21.1 Tuberculosis screening21.2 Toxoplasma serology21.3 Tropical screening21.4 References22. Sexual health screening including anal and cervical cytology22.1 Sexual history taking, counselling and sexually transmitted infection (STI) screening22.2 Cervical and anal cytology22.3 Recommendations22.4 References23. Routine monitoring recommended for specific patient groups23.1 Women23.2 Older age23.3 Injecting drug users23.4 Individuals coinfected with HBV and HCV23.5 Late presenters23.6 References Appendix