Insights into long-term mortality, especially into the cause of death after initial recovery from an episode of community-acquired pneumonia (CAP), may help in determining optimal preventive measures in such patients. Prospective observational cohort studies were conducted to compare cause-specific long-term mortality rates for 356 patients who had recovered from CAP with those of the general Dutch population (16.3 million) between 2003 and 2007. The Dutch Municipal Public Records Database and death certificates were used to determine cause-specific mortality rates up to 7 years after discharge. In patients who had recovered from CAP, cumulative 1-year, 5-year and 7-year mortality rates were 17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age-matched and sex-matched population reference cohort. Overall, patients who had recovered from CAP had significantly higher long-term mortality than matched population controls (rate ratio (RR) 3.6; p <0.001). In the years after an episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD) (19%) and cardiovascular disease (16%) were the most frequent causes of death. Only 6% died of pneumonia, as compared with 3.2% in the general population. After initial recovery from an episode of CAP, long-term mortality rates are more than three times as high as in the general population. The causes of long-term mortality were mostly comorbidity-related, and significantly different from those in the general population. After an episode of CAP, optimization of treatment of comorbidities, such as treatment for COPD, might improve long-term survival rates.

BACKGROUNDChest radiographs are often used to diagnose community-acquired pneumonia (CAP), to monitor response to treatment and to ensure complete resolution of pneumonia. However, radiological exams may not reflect the actual clinical condition of the patient.OBJECTIVETo compare the radiographic resolution of mild to moderately severe CAP to resolution of clinical symptoms as assessed by the physician or rated by the patient.DESIGNProspective cohort study.PARTICIPANTSOne hundred nineteen patients admitted because of mild to moderately severe CAP with new pulmonary opacities.MAIN MEASURESRadiographic resolution and clinical cure of CAP were determined at day 10 and 28. Radiographic resolution was defined as the absence of infection-related abnormalities; clinical cure was rated by the physician and defined by improvement of signs and symptoms. In addition, the CAP score, a patient-based symptom score, was calculated.KEY RESULTSRadiographic resolution, clinical cure and normalization of the CAP score were observed in 30.8%, 93% and 32% of patients at day 10, and in 68.4%, 88.9% and 41.7% at day 28, respectively. More severe CAP (PSI score >90) was independently associated with delayed radiographic resolution at day 28 (OR 4.7, 95% CI 1.3–16.9). All 12 patients with deterioration of radiographic findings during follow-up had clinical evidence of treatment failure.CONCLUSIONSIn mild to moderately severe CAP, resolution of radiographic abnormalities and resolution of symptoms scored by the patient lag behind clinical cure assessed by physicians. Monitoring a favorable disease process by routine follow-up chest radiographs seems to have no additional value above following a patient's clinical course.

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We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Background. Timing of follow-up chest radiographs for patients with severe community-acquired pneumonia (CAP) is difficult, because little is known about the time to resolution of chest radiograph abnormalities and its correlation with clinical findings. To provide recommendations for short-term, in-hospital chest radiograph followup, we studied the rate of resolution of chest radiograph abnormalities in relation to clinical cure, evaluated predictors for delayed resolution, and determined the influence of deterioration of radiographic findings during follow-up on prognosis.Methods. A total of 288 patients who were hospitalized because of severe CAP were followed up for 28 days in a prospective multicenter study. Clinical data and scores for clinical improvement at day 7 and clinical cure at day 28 were obtained. Chest radiographs were obtained at hospital admission and at days 7 and 28. Resolution and deterioration of chest radiograph findings were determined.Results. At day 7, 57 (25%) of the patients had resolution of chest radiograph abnormalities, whereas 127 (56%) had clinical improvement (mean difference, 31%; 95% confidence interval, 25%-37%). At day 28, 103 (53%) of the patients had resolution of chest radiograph abnormalities, and 152 (78%) had clinical cure (mean difference, 25%; 95% confidence interval, 19%-31%). Delayed resolution of radiograph abnormalities was independently associated with multilobar disease (odds ratio, 2.87; ); dullness to percussion at physical ex-P р .01 amination (odds ratio, 6.94;); high C-reactive protein level, defined as 1200 mg/L (odds ratio, 4.24; P р .01 ); and high respiratory rate at admission, defined as 125 breaths/min (odds ratio, 2.42;). There P р .001 P р .03 were no significant differences in outcome at day 28 between patients with and patients without deterioration of chest radiograph findings during the follow-up period ( ). P 1 .09 Conclusions. Routine short-term follow-up chest radiographs (obtained !28 days after hospital admission) of hospitalized patients with severe CAP seem to provide no additional clinical value.

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Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44–60] years, 85.5% male) and 440 controls (median age 43 [IQR 33–53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520–913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322–1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508–0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250–500 cells/μL (2.845, 95% CI 1.876–4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961–4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286–0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.

Background The COVIH-study is a prospective SARS-CoV-2 vaccination study in 1154 people with HIV (PWH), of whom 14% showed a reduced or absent antibody response after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. Methods Consenting hyporesponders received an additional 100µg mRNA-1273 vaccination. The primary endpoint was the increase in antibodies 28 days thereafter. Secondary endpoints were the correlation between participant characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Results Of the 66 participants, 40 previously received two doses ChAdOx1-S, 22 two doses BNT162b2, and four a single dose Ad26.COV2.S. The median age was 63[IQR:60-66], 86% were male, pre-vaccination CD4+ T-cell count was median 650/μL[IQR:423-941] and 96% had HIV-RNA &lt; 50 copies/mL. The mean S1-specific antibody level increased from 35 BAU/mL (95%CI:24–46) to 4317 BAU/mL (95%CI:3275–5360) post-vaccination (p &lt; 0.0001). Of all participants, 97% showed an adequate response (&gt;300 BAU/mL) and the 45 antibody negative participants all seroconverted (&gt;33.8 BAU/mL). A significant increase in the proportion of PWH with detectable ancestral S-specific CD4+ T-cells (p = 0.04) and S-specific B-cells (p = 0.02) was observed. Conclusion An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.