An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

Background. There is limited information about clinical consequences of respiratory virus infections (RVI) in solid organ transplant recipients. No prospective epidemiological study has been published previously. Methods. We selected a cohort of 152 transplant recipients (cardiac, hepatic and renal transplant recipients). Median time from transplantation was 17 months (range 1–50). They were prospectively followed-up for RVI during 7 months (October to April). Clinical and microbiological evaluation (cell culture, shell vial and polymerase chain reaction technique) of each RVI episode was made. Results. We detected 81 RVI (0.91 episodes/patient/year). Complications were detected in 15/81 episodes (18.5%): acute bronchitis (10 cases), pneumonia (three cases; 3.7% of RVI episodes) and bacterial sinusitis (2 cases). In 4 of 81 episodes (5%), patients needed hospitalization. A respiratory virus was isolated in 17 of 68 nasopharyngeal samples (six respiratory syncytial virus, six influenza, four picornavirus, one adenovirus). Fever presented an 83% positive predictive value for the diagnosis of influenza virus infection among those with a positive microbiological isolation. There were no episodes of acute rejection coincidentally with RVI. Only 54% of the subjects had been previously vaccinated against influenza. Conclusions. Incidence of RVI among solid organ transplant recipients is similar to general population but complications are higher. A relationship between RVI and rejection was not detected. The rate of influenza vaccination was lower than expected. The presence of fever in a transplant recipient with RVI strongly suggests influenza infection.

The risk of opportunistic infection (OI) is considered to be maximum during the first six months after solid organ transplantation. The aim of this study was to know the incidence and risk factors for OI in the late period (>6 months) compared with the early period (<6 months) after solid organ transplantation. We used the online database of the Spanish Network of Infection in Transplantation (RESITRA), which prospectively analyzed 2,702 solid organ transplantation recipients from August 2003 to February 2005. Univariate and multivariate analyses were performed to calculate the risk factors associated with the development of late OI. A total of 131 patients (6%) developed 176 infectious episodes in the late period. Although the incidence of infection and cytomegalovirus disease (0.4 per 1000 transplant days and 0.05 per 1000 transplant days, respectively) was lower than in the early period (3.5 per 1000 transplant days and 0.8 per 1000 transplant days; P<0.0001), the incidence of other OIs was similar in both periods (0.05 per 1000 transplant days versus 0.03 per 1000 transplant-days, P=0.5). Patients with the higher risk for developing late OI were those receiving early cytomegalovirus prophylaxis, patients who developed two or more episodes of acute rejection during the early period, patients with recurrent bacterial infection during the early period, patients with renal failure requiring dialysis, and patients with chronic graft malfunction. Our data suggest that in some high-risk patients, the critical period of risk for OI must be expanded beyond the first six months after transplant.

The role of valganciclovir in the prevention of cytomegalovirus (CMV) disease in high-risk seropositive transplant patients is not known. We prospectively followed 301 seropositive solid organ transplant recipients to assess the efficacy and safety of valganciclovir (VGCV) in the prevention of CMV disease in high-risk patients. Asymptomatic patients with an antigenemia test >or=25 positive cells/2x10(5) polymorphonuclear cells received valganciclovir 900 mg twice a day as preemptive therapy until resolution of antigenemia (minimum 14 days). Additionally, patients treated with antilymphocytic drugs for more than 6 days received prophylaxis with VGCV 900 mg once a day during 90 days. Mean follow-up was 14 months (range 6-20 months). Thirty-eight patients received VGCV; 24 as preemptive therapy and 14 due to the use of antilymphocytic drugs. No patient developed CMV disease during the follow-up. Viral load (antigenemia) decreased a mean of 78% from baseline after 7 days of VGCV therapy (P=0.024) and 98% at day 14 (P=0.029). Two patients showed a relapse of the antigenemia test >or=25 positive cells and were successfully treated with a repeated course of VGCV. Leukopenia (<2500/mm3) developed in 3/24 (12.5%) recipients in the preemptive therapy group and required to discontinuing the drug in one of them. VGCV is safe and highly efficacious in the prevention of CMV disease in high-risk seropositive organ transplant recipients.