Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial.

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.

Global Trends of Monitoring and Data Collection on the HIV Response among Key Populations Since the 2001 UN Declaration of Commitment on HIV/AIDS.

Monitoring and evaluation indicators for HIV programs' response to the epidemic among key populations (sex workers, people who inject drugs, men who have sex with men, transgender people) are critical for reviewing the global response. From the beginning of global reporting, insufficiency of data has been a challenge for monitoring the epidemic response among key populations. However, key populations were only indirectly referenced in the 2001 Declaration of Commitment. By the 2006 Political Declaration on HIV/AIDS, data from key populations were still not required from every country, and were sparsely reported compared to other indicators. The 2011 Political Declaration on HIV/AIDS referenced key populations by name for the first time. In 2006, fewer than twenty countries (10%) reported HIV prevalence among key populations, whereas in 2012 the number of countries surpassed sixty (30%).

Effective use of naloxone among people who inject drugs in Kyrgyzstan and Tajikistan using pharmacy- and community-based distribution approaches.

BACKGROUND: Opioid overdose (OD) is a major cause of mortality among people who inject drugs (PWID) in Central Asia, and distribution of naloxone, an opioid antagonist, can effectively prevent these deaths. However, little is known about the use and wastage of distributed naloxone ampoules. Having reliable data on wastage rates is critical for accurately calculating the health impact of naloxone distribution projects targeting PWID. METHODS: In 2011, Population Services International (PSI) launched two pilot naloxone distribution programs in Kyrgyzstan (pharmacy-based approach) and Tajikistan (community-based approach). PWID were trained on OD prevention and naloxone use. Upon returning for more ampoules, the PWID completed a brief survey on their OD experience and naloxone use. 158 respondents in Kyrgyzstan and 59 in Tajikistan completed the questionnaire. Usage and wastage rates were calculated based on responses. A four-year model wastage rate that takes into account the shelf life of naloxone for both countries was then calculated. RESULTS: 51.3% of respondents in Kyrgyzstan and 91.5% in Tajikistan reported having ever experienced an OD. 82.9% of respondents in Kyrgyzstan and all respondents in Tajikistan had ever witnessed an OD. Out of these PWID who experienced or witnessed OD, 81.5% in Kyrgyzstan and 59.3% in Tajikistan reported having been injected with naloxone, and 83.2% in Kyrgyzstan and 50.9% in Tajikistan reported injecting another individual with naloxone. Of ampoules received, 46.5% in Kyrgyzstan and 78.1% in Tajikistan were used. In both countries, 3.1% of these ampoules were wasted. The four-year model wastage rates for Kyrgyzstan and Tajikistan were found to be 13.8% and 3.9% respectively. CONCLUSION: Findings indicate that a high proportion of naloxone distributed to PWID is used in actual OD incidents, with low wastage rates in both countries. Expanding these distribution models can potentially create more positive health outcomes for PWID in Central Asia.

Clamping down on weak terminal base pairs: oligonucleotides with molecular caps as fidelity-enhancing elements at the 5'- and 3'-terminal residues.

The base-pairing fidelity of oligonucleotides depends on the identity of the nucleobases involved and the position of matched or mismatched base pairs in the duplex. Nucleobases forming weak base pairs, as well as a terminal position favor mispairing. We have searched for 5'-appended acylamido caps that enhance the stability and base-pairing fidelity of oligonucleotides with a 5'-terminal 2'-deoxyadenosine residue using combinatorial synthesis and MALDI-monitored nuclease selections. This provided the residue of 4-(pyren-1-yl)butyric acid as a lead. Lead optimization gave (S)-N-(pyren-1-ylmethyl)pyrrolidine-3-phosphate as a cap that increases duplex stability and base-pairing fidelity. For the duplex of 5'-AGGTTGAC-3' with its fully complementary target, this cap gives an increase in the UV melting point T(m) of +10.9 degrees C. The T(m) is 6.3-8.3 degrees C lower when a mismatched nucleobase faces the 5'-terminal dA residue. The optimized cap can be introduced via automated DNA synthesis. It was combined with an anthraquinone carboxylic acid residue as a cap for the 3'-terminal residue. A doubly capped dodecamer thus prepared gives a melting point decrease for double-terminal mismatches that is 5.7-5.9 degrees C greater than that for the unmodified control duplex.