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A reemergence of parvovirus B19 infections in Spain in early 2024 prompted a 10-year review of the virus at a tertiary center. We identified 8 case-patients with neurologic manifestations who had parvovirus B19 in cerebrospinal fluid. Early recognition and management of parvovirus B19-associated neurologic conditions will help yield favorable outcomes.

Background COVID-19 diagnosis lies on the detection of SARS-CoV-2 on nasopharyngeal specimens by RT-PCR. The Xpert-Xpress SARS-CoV-2 assay provides results in less than one hour from specimen reception, which makes it suitable for clinical/epidemiological circumstances that require faster responses. The analysis of a COVID-19 outbreak suspected in the neonatology ward from our institution showed that the Ct values obtained for the targeted genes in the Xpert assay were markedly different within each specimen (N Ct value > 20 cycles above the E Ct value). Results We identified the mutation C29200T in the N gene as responsible for an impairment in the N gene amplification by performing whole genome sequencing of the specimens involved in the outbreak (Omicron variant). Subsequently, a retrospective analysis of all specimens sequenced in our institution allowed us to identify the same SNP as responsible for similar impairments in another 12 cases (42% of the total cases reported in the literature). Finally, we found that the same SNP emerged in five different lineages independently, throughout almost all the COVID-19 pandemic. Conclusions We demonstrated for the first time the impact of this SNP on the Xpert assay, when harbored by new Omicron variants. We extend our observation period throughout almost all the COVID-19 pandemic, offering the most updated observations of this phenomenon, including sequences from the seventh pandemic wave, until now absent in the reports related to this issue. Continuous monitoring of emerging SNPs that could affect the performance of the most commonly used diagnostic tests, is required to redesign the tests to restore their correct performance.

Centers for Disease Control and Prevention guidelines consider SARS-CoV-2 reinfection when sequential COVID-19 episodes occur >90 days apart. However, genomic diversity acquired over recent COVID-19 waves could mean previous infection provides insufficient cross-protection. We used genomic analysis to assess the percentage of early reinfections in a sample of 26 patients with 2 COVID-19 episodes separated by 20-45 days. Among sampled patients, 11 (42%) had reinfections involving different SARS-CoV-2 variants or subvariants. Another 4 cases were probable reinfections; 3 involved different strains from the same lineage or sublineage. Host genomic analysis confirmed the 2 sequential specimens belonged to the same patient. Among all reinfections, 36.4% involved non-Omicron, then Omicron lineages. Early reinfections showed no specific clinical patterns; 45% were among unvaccinated or incompletely vaccinated persons, 27% were among persons <18 years of age, and 64% of patients had no risk factors. Time between sequential positive SARS-CoV-2 PCRs to consider reinfection should be re-evaluated.

Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients entails high mortality and requires adequate laboratory diagnosis. We compared the performance of a real time-PCR assay against the immunofluorescence assay (IFA) in the routine of a large microbiology laboratory. Different respiratory samples from HIV and non-HIV-infected patients were included. The retrospective analysis used data from September 2015 to April 2018, which included all samples for which a P. jirovecii test was requested. A total of 299 respiratory samples were tested (bronchoalveolar lavage fluid (n = 181), tracheal aspirate (n = 53) and sputum (n = 65)). Forty-eight (16.1%) patients fulfilled the criteria for PJP. Five positive samples (10%) had only colonization. The PCR test was found to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96%, 98%, 90% and 99%, compared to 27%, 100%, 100% and 87%, for the IFA, respectively. PJ-PCR sensitivity and specificity were >80% and >90% for all tested respiratory samples. Median cycle threshold values in definite PJP cases were 30 versus 37 in colonized cases (p < 0.05). Thus, the PCR assay is a robust and reliable test for the diagnosis PJP in all respiratory sample types. Ct values of ≥36 could help to exclude PJP diagnosis.

Background SARS-CoV-2 recombinants involving the divergent Delta and Omicron lineages have been described, and one of them, “Kraken” (XBB.1.5), has recently been a matter of concern. Recombination requires the coexistence of two SARS-CoV-2 strains in the same individual. Only a limited number of studies have focused on the identification of co-infections and are restricted to co-infections involving the Delta/Omicron lineages. Methods We performed a systematic identification of SARS-CoV-2 co-infections throughout the pandemic (7609 different patients sequenced), not biassed towards the involvement of highly divergent lineages. Through a comprehensive set of validations based on the distribution of allelic frequencies, phylogenetic consistency, re-sequencing, host genetic analysis and contextual epidemiological analysis, these co-infections were robustly assigned. Results Fourteen (0.18%) co-infections with ≥ 8 heterozygous calls (8–85 HZs) were identified. Co-infections were identified throughout the pandemic and involved an equal proportion of strains from different lineages/sublineages (including pre-Alpha variants, Delta and Omicron) or strains from the same lineage. Co-infected cases were mainly unvaccinated, with mild or asymptomatic clinical presentation, and most were at risk of overexposure associated with the healthcare environment. Strain segregation enabled integration of sequences to clarify nosocomial outbreaks where analysis had been impaired due to co-infection. Conclusions Co-infection cases were identified throughout the pandemic, not just in the time periods when highly divergent lineages were co-circulating. Co-infections involving different lineages or strains from the same lineage were occurring in the same proportion. Most cases were mild, did not require medical assistance and were not vaccinated, and a large proportion were associated with the hospital environment.

Background There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation. Methods We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use). Results We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39–67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01). Conclusions In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.

Since the COVID-19 outbreak, specific mRNA-based anti-SARS-CoV-2 vaccines have been developed and distributed worldwide. Because this is the first time that mRNA vaccines have been used, there are several questions regarding their capacity to confer immunity and the durability of the specific anti-SARS-CoV-2 response. Therefore, the objective of this study was to recruit a large cohort of healthcare workers from the Gregorio Marañón Hospital vaccinated with the mRNA-1273 or BNT126b2 vaccines and to follow-up on IgG anti-RBD levels at 8 months post-vaccination. We recruited 4,970 volunteers and measured IgG anti-RBD antibodies on days 30 and 240 post-vaccination. We observed that both vaccines induced high levels of antibodies on day 30, while a drastic wane was observed on day 240, where mRNA-1273 vaccinated induced higher levels than BNT162b2. Stratifying by vaccine type, age, gender, and comorbidities, we identified that older mRNA-1273-vaccinated volunteers had higher antibody levels than the younger volunteers, contrary to what was observed in the BNT162b2-vaccinated volunteers. In conclusion, we observed that mRNA-1273 has a higher capacity to induce a humoral response than BNT162b2 and that age is a factor in the specific response.

There is limited data on the efficacy of combined antiviral treatment for immunosuppressed COVID-19 patients. We describe the clinical and microbiological outcomes of a cohort of oncohaematological patients with persistent SARS-CoV-2 infection who received different dual and triple antiviral combination treatments. We selected the 15 patients (two of them with two episodes) who were prescribed combined anti-SARS-CoV-2 treatment in our institution (October 2021–December 2024). Combined antiviral therapy was administered as a compassionate use in the following indications: (i) persistence of SARS-CoV-2 positive quantitative RT-PCR (qRT-PCR) for > 14 days despite antiviral monotherapy and severe COVID-19 or (ii) need to achieve viral clearance before hematopoietic progenitor transplantation or administration of immuno-chemotherapy. Samples corresponding to positive qRT-PCR results with a Ct value < 32 were analysed by whole-genome sequencing. In 13 out of a total of 15 episodes, with control qRT-PCR after the combination therapy, with positivity periods ranging from 12 to 235 days, viral clearance was achieved 10–69 days after receiving the combination therapy. Whole genome sequencing revealed the emergence of resistance mutations in three cases prior to combination therapy. The therapy was able to overcome these mutations and lead to clearance. Genomic analysis identified one patient with three consecutive reinfections that had been mismanaged as persistent infection. In conclusion, combined antiviral treatment leads to satisfactory clinical and microbiological outcomes in a small cohort of immunocompromised patients with persistent SARS-CoV-2 infection. Early monotherapy treatment in these patients was associated with a high rate of clinical and microbiological failure, with sporadic documentation of resistance mutations that were overcome with combined antiviral therapy.

Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients entails high mortality and requires adequate laboratory diagnosis. We compared the performance of a real time-PCR assay against the immunofluorescence assay (IFA) in the routine of a large microbiology laboratory. Different respiratory samples from HIV and non-HIV-infected patients were included. The retrospective analysis used data from September 2015 to April 2018, which included all samples for which a P. jirovecii test was requested. A total of 299 respiratory samples were tested (bronchoalveolar lavage fluid (n = 181), tracheal aspirate (n = 53) and sputum (n = 65)). Forty-eight (16.1%) patients fulfilled the criteria for PJP. Five positive samples (10%) had only colonization. The PCR test was found to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96%, 98%, 90% and 99%, compared to 27%, 100%, 100% and 87%, for the IFA, respectively. PJ-PCR sensitivity and specificity were >80% and >90% for all tested respiratory samples. Median cycle threshold values in definite PJP cases were 30 versus 37 in colonized cases (p < 0.05). Thus, the PCR assay is a robust and reliable test for the diagnosis PJP in all respiratory sample types. Ct values of ≥36 could help to exclude PJP diagnosis.