Conformational stability of SARS-CoV-2 glycoprotein spike variants.

The severe acute respiratory syndrome spread worldwide, causing a pandemic. SARS-CoV-2 mutations have arisen in the spike, a glycoprotein at the viral envelope and an antigenic candidate for vaccines against COVID-19. Here, we present comparative data of the glycosylated full-length ancestral and D614G spike together with three other transmissible strains classified by the World Health Organization as variants of concern: beta, gamma, and delta. By showing that D614G has less hydrophobic surface exposure and trimer persistence, we place D614G with features that support a model of temporary fitness advantage for virus spillover. Further, during the SARS-CoV-2 adaptation, the spike accumulates alterations leading to less structural stability for some variants. The decreased trimer stability of the ancestral and gamma and the presence of D614G uncoupled conformations mean higher ACE-2 affinities compared to the beta and delta strains. Mapping the energetics and flexibility of variants is necessary to improve vaccine development.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

On the efficacy of online drug surveys during the time of COVID-19

Most human subjects research involving contact with participants has been halted in the US due to the COVID-19 crisis. We have been testing an online method to recruit and survey participants as a temporary replacement for our street-intercept survey method. Online surveys already generate less generalizable findings than other surveys, but offering compensation for online survey completion further reduces generalizability because this increases mischievous submissions. In this letter we discuss methods to help detect invalid responses, such as utilizing a screener to test for eligibility and using flags to detect mischievous responses and repeat submissions. We recommend that researchers approach online recruitment and surveying with caution.

Virtual raves and happy hours during COVID-19: New drug use contexts for electronic dance music partygoers.

BACKGROUND: The popularity of virtual raves and happy hours has increased during the COVID-19 pandemic. While nightlife settings are often associated with drug use, it is unknown whether virtual events are associated with use. METHODS: Electronic dance music (EDM) partygoers who live in New York and reported recent drug use were recruited online and screened for eligibility throughout April and May 2020. Eligible adults (n = 128) were asked about virtual rave and happy hour attendance during the COVID-19 crisis. We examined prevalence and correlates of drug use during such events. RESULTS: 55.5% of participants attended virtual raves and 69.5% attended virtual happy hours. 40.9% used illegal drugs during virtual raves and the most frequently used drugs were cannabis (29.6%), ecstasy/MDMA/Molly (8.5%), LSD (7.0%), and cocaine (4.2%). 33.7% used illegal drugs during virtual happy hours and the most frequently used drugs were cannabis (29.2%), cocaine (3.4%), and ketamine (3.4%). Older participants were more likely to use illegal drugs during virtual raves, and those reporting past-year use of more drugs were more likely to use drugs during virtual raves and/or happy hours (ps<0.05). CONCLUSIONS: EDM partygoers are at risk for using drugs during virtual events. Results can inform prevention and harm reduction efforts.

Shifts in Drug Use Behavior Among Electronic Dance Music Partygoers in New York During COVID-19 Social Distancing.

Background: Little is known about how COVID-19-related social distancing has affected illegal drug use. We surveyed electronic dance music (EDM) partygoers-a population known for high levels of drug use-to determine whether their drug use patterns had changed during state-mandated social distancing in New York. Methods: Individuals were recruited online and screened for eligibility throughout April and May 2020. We surveyed 128 eligible adults and queried, retrospectively, whether their drug use behavior had changed during COVID-19-related social distancing. Results: Most participants reporting past-three-month use reported decreased frequency of use during COVID-19-related social distancing. Specifically, 78.6% reduced frequency of use of cocaine, 71.1% reduced frequency of use of ecstasy/MDMA/Molly, and 68.0% reduced frequency of use of LSD. Although some participants reported increased frequency of use of cocaine (7.1%), ecstasy (7.9%), or LSD (12.0%), 35.0% reported increased frequency of cannabis use. Most (66.7%) of those reporting cocaine use reduced the amount used. The majority of those reporting use of cannabis, ecstasy, cocaine, and/or LSD reported that drug cost (80.0-84.0%) and drug quality (84.2-92.0%) did not change during social distancing. Having a college degree was associated with higher odds for decreasing frequency of cannabis use. Older participants (ages ≥23) were at lower odds for decreasing frequency of cocaine use, as were those earning >$500 per week, and participants who attended EDM events biweekly or more often were at higher odds for decreasing frequency of LSD use. Conclusions: Participants in this sample tended to reduce party drug use during COVID-19-related social distancing.

On the efficacy of online drug surveys during the time of COVID-19.

Most human subjects research involving contact with participants has been halted in the US due to the COVID-19 crisis. We have been testing an online method to recruit and survey participants as a temporary replacement for our street-intercept survey method. Online surveys already generate less generalizable findings than other surveys, but offering compensation for online survey completion further reduces generalizability because this increases mischievous submissions. In this letter we discuss methods to help detect invalid responses, such as utilizing a screener to test for eligibility and using flags to detect mischievous responses and repeat submissions. We recommend that researchers approach online recruitment and surveying with caution.