Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients’ characteristics.

The objective of this study was to assess the association between patients’ epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients’ underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age > 60 years (pOR 3.50; 95% CI 2.97–4.36), smoking habit (pOR 3.50; 95% CI 2.97–4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14–4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92–4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59–4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97–3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83–4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35–4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61–3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients’ characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment.

A phase 2 trial was conducted to evaluate the safety and efficacy of convalescent plasma (CP) for patients admitted with COVID-19 in the pre-vaccine era. CP was compared to standard of care (SoC) in a randomized clinical trial in patients admitted with COVID-19 pneumonia and with either hypoxia and/or some underlying condition from April to December 2020 in 15 hospitals in Andalusia, Spain. The primary endpoints were adverse events and failure (all-cause death and need for mechanical ventilation during the first 21 days). The procedure for CP was developed and worked properly. Overall, 72 patients of 88 evaluated were recruited (37 and 35) assigned to CP and SoC. Median duration of COVID-19 related symptoms was 7 and 6 days, and median oxygen saturation at randomization was 93% and 92.5% in experimental and control arms, respectively. Overall, 8 (21.6%) patients in the experimental CP group (non related to CP) and 8 (22.9%) in the control group developed grade 3 adverse events (relative risk [RR] 0.94; 95% CI: 0.39-2.24); failure occurred in 3 (8.1%) and 4 (11.4%) patients, respectively ([RR] 0.94, CI: 0.14-6.35 for both events). No differences in secondary endpoints (change in inflammatory parameters, negativization of SARS-CoV-2 PCR or duration of hospital stay) were found. The results suggested that CP is safe for use in COVID-19 patients, although no significant efficacy signal could be observed. A successful regional system for CP administration was developed.

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes.