Long-term stability of picocyanobacteria in the open oceans is maintained by a balance between synchronous division and death on daily timescales. Viruses are considered a major source of microbial mortality, however, current methods to measure infection have significant methodological limitations. Here we describe a method that pairs flow-cytometric sorting with a PCR-based polony technique to simultaneously screen thousands of taxonomically resolved individual cells for intracellular virus DNA, enabling sensitive, high-throughput, and direct quantification of infection by different virus lineages. Under controlled conditions with picocyanobacteria-cyanophage models, the method detected infection throughout the lytic cycle and discriminated between varying infection levels. In North Pacific subtropical surface waters, the method revealed that only a small percentage of Prochlorococcus (0.35–1.6%) were infected, predominantly by T4-like cyanophages, and that infection oscillated 2-fold in phase with the diel cycle. This corresponds to 0.35–4.8% of Prochlorococcus mortality daily. Cyanophages were 2–4-fold more abundant than Prochlorococcus, indicating that most encounters did not result in infection and suggesting infection is mitigated via host resistance, reduced phage infectivity and inefficient adsorption. This method will enable quantification of infection for key microbial taxa across oceanic regimes and will help determine the extent that viruses shape microbial communities and ecosystem level processes.

BackgroundThe risk of infections among patients with psoriasis undergoing interleukin (IL)‐23 inhibitors (IL‐23i) and IL‐17 inhibitors (IL‐17i) is yet to be exhaustively determined.ObjectiveTo assess the risk of infectious complications in patients with psoriasis managed by IL‐23i and IL‐17i with tumour necrosis factor inhibitors (TNFi) as a comparator.MethodsA global cohort study comprised two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL‐23i (n = 5272) versus TNFi (n = 5272) and (ii) new users of IL‐17i (n = 15,160) versus TNFi (n = 15,160). Study groups were compared regarding the risk of 26 different infections. Propensity score matching was conducted to optimize between‐group comparability.ResultsPatients under IL‐23i had a lower risk of otitis media (HR, 0.66; 95% CI, 0.44–0.97), encephalitis (HR, 0.18; 95% CI, 0.04–0.78), herpes zoster (HZ; HR, 0.58; 95% CI, 0.41–0.82), hepatitis B virus (HBV) reactivation (HR, 0.24; 95% CI, 0.12–0.47), cytomegalovirus (HR, 0.25; 95% CI, 0.07–0.86), influenza (HR, 0.52; 95% CI, 0.38–0.71) and parasitic diseases (HR, 0.78; 95% CI, 0.64–0.95). IL‐17i was associated with a decreased risk of pneumonia (HR, 0.76; 95% CI, 0.68–0.85), septicaemia (HR, 0.84; 95% CI, 0.72–0.97), upper respiratory tract infection (HR, 0.84; 95% CI, 0.77–0.92), HZ (HR, 0.79; 95% CI, 0.67–0.92), HBV (HR, 0.59; 95% CI, 0.46–0.76) and hepatitis C virus (HR, 0.71; 95% CI, 0.57–0.88) reactivation, cytomegalovirus (HR, 0.58; 95% CI, 0.36–0.93), Epstein–Barr virus (HR, 0.38; 95% CI, 0.19–0.75), influenza (HR, 0.70; 95% CI, 0.61–0.81) and parasitic diseases (HR, 0.80; 95% CI, 0.72–0.88).ConclusionCompared with TNFi, IL‐23i and IL‐17i are associated with decreased risk of several infectious diseases. These agents might be preferred in patients with susceptibility to infections.

Background The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated. Objective To evaluate the risk of infections in patients with pemphigus managed by rituximab versus first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]). Methods A global population-based cohort study compared pemphigus patients initiating rituximab (n = 963) versus azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability. Results In the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.06-3.14; P = 0.028), parasitic diseases (HR, 3.22; 95% CI, 1.04-9.97; P = 0.032), and cytomegalovirus infection (HR, 1.63; 95% CI, 1.04-2.58; P = 0.033). When evaluating infections developing ≥12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR, 1.45; 95% CI, 1.00-2.10; P = 0.047), COVID-19 (HR, 1.87; 95% CI, 1.49-2.33; P < 0.001), osteomyelitis (HR, 2.42; 95% CI, 1.11-5.31; P = 0.023), herpes simplex (HR, 2.06; 95% CI, 1.03-4.11; P = 0.037), and cytomegalovirus (HR, 1.63; 95% CI, 1.07-2.49; P = 0.023) infections. Conclusion Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis, and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even one year following therapy. No signal for elevated risk of tuberculosis, hepatitis B virus reactivation, pneumocystis jiroveci pneumonia, and progressive multifocal leukoencephalopathy

Dear Editor, Robust evidence suggests that psoriasis is associated with an elevated risk of cardiovascular diseases, which embody the most common cause of morbidity and mortality amongst patients with psoriasis. 1,2 Whilst biologic agents undoubtedly led to a groundbreaking improvement in patient care and optimized patient outcomes, 3 their effect on cardiovascular outcomes in psoriasis is a scope of controversy. 4-6 A meta-analysis pooling 38 randomized controlled trials detected no significant influence of biologics on the incidence of major adverse cardiovascular events (MACE) in patients with psoriasis. 7 Interleukin (IL)-17 inhibitors (IL-17i) and IL-23 inhibitors (IL-23i) emerged as promising therapeutic options in psoriasis, guaranteeing high efficacy and long-term maintenance of treatment response. 8,9 The aim of the current study is to investigate the risk of cardiovascular and metabolic outcomes amongst patients with psoriasis initiating IL-23i versus IL-17i using a large-scale real-life observational study.Based on the TriNetX database, the current study was designed as a global, population-based, retrospective cohort study that longitudinally follows patients with psoriasis initiating IL-23i and IL-17i to track the risk of cardiovascular and metabolic outcomes. Medical files of all 117.5 million health-insured individuals in the Global Collaborative Network were systematically screened for a diagnostic code compatible with psoriasis. Two treatment groups of patients with psoriasis were allocated. The first included patients initiating any of the following IL-23i agents: risankizumab, guselkumab and tildrakizumab. The second group encompassed patients starting IL-17i treatment, including any of the following agents: secukinumab, ixekizumab and brodalumab. To be eligible for inclusion in the first group, patients were ascertained to lack any preexisting or subsequent exposure to IL-17i. Similarly, Patients in the second group had to lack any lifetime prescription of IL-23i.Propensity score matching was conducted to balance the two study groups. Matching was carried out based on demographic variables, some confounding comorbidities, family history of ischemic heart disease and other diseases of the circulatory system, stroke and diabetes mellitus and previous exposure to different treatment modalities (Table 1). Participants in both groups were followed longitudinally to evaluate the risk of developing 11 different cardiovascular and metabolic outcomes.

ImportanceThe association of different therapeutic approaches with long-term cardiovascular and metabolic outcomes in patients with pemphigus remains to be precisely evaluated.ObjectiveTo assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab compared with those receiving treatment with first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]).Design, Setting, and ParticipantsA global population–based retrospective cohort study compared 961 patients with pemphigus that was managed with rituximab with those treated with azathioprine or MMF (n = 961) regarding the risk of several cardiovascular and metabolic outcomes. Propensity score matching was performed to optimize comparability. Patients were enrolled from the Global Collaborative Network of TriNetX platform.Main Outcomes and MeasuresRisk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis.ResultsOf 1602 participants, 855 (53.4%) were women and 747 (46.6%) were men; the mean (SD) age was 54.8 (16.6) years for those treated with rituximab and 54.4 (18.2) years for those treated with azathioprine or MMF. Compared with those treated by azathioprine/MMF, patients treated with rituximab experienced a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P < .001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P < .001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P < .001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P < .001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P < .001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P < .001). The all-cause mortality was comparable between patients in both groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P = .77).Conclusions and RelevanceThe results of this cohort study suggest that rituximab was associated with protection against long-term cardiovascular and metabolic outcomes compared with conventional immunosuppressants. This agent might be particularly preferred in individuals with preexisting cardiovascular and metabolic risk factors.

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