ABSTRACT
BackgroundVaccines against SARS-CoV-2 have provided an invaluable resource in the fight against this infection. Given the current vaccine shortage, vaccination programs must prioritize their distribution to the most appropriate segments of the population. MethodsWe carried out a prospective cohort study with 63 health care workers (HCWs) from a public General Hospital. We compared antibody responses to two doses of BNT162b2 mRNA Covid-19 vaccine between HCWs with laboratory-confirmed SARS-CoV-2 infection before vaccination (experienced HCWs) and HCWs who were not previously infected (naive HCWs). ResultsSeven days after the first vaccine dose HCWs with previous infection experienced a 126 fold increase in antibody levels (GMC 26955 AU; 95% CI 18785-35125). However, in the HCW naive group the response was much lower and only 5 of them showed positive antibody levels (>50 AU). The HCWs with previous infection did not significantly increased their antibody levels after the second dose while there was a significant increase in the naive HCW group (16 fold; GMC 20227 AU; 95% CI: 15179-25275). Approximately two months after completing vaccination, the level of antibodies was much lower in naive HCWs (GMC 6595 AU vs. 25003 AU; p<0.001) ConclusionThe study shows that 10 months after the disease has passed, the immune system is capable of producing a rapid and powerful secondary antibody response after one single dose of the vaccine. This response reflects the persistence of immunological memory and it is independent of whether or not anti-SARS-CoV-2 antibodies are detected in blood. Besides, we found that the second dose does not improve the antibody response in individuals with previous Covid-19 infection. Nonetheless, two months later, the persistence of antibody levels is still higher in the experienced HCWs. These data suggest that immune memory remains for a long time in recovered individuals, and therefore, vaccination in this group could be postponed until immunization of the rest of the population is complete.
ABSTRACT
Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.
