Calvo-Silveria Sara, Fernández-Delgado Lucía, González-Díaz Aida, España-Bonilla Rocío, Calatayud Laura, Niubó Jordi, Martí Sara, Domínguez Ma Ángeles, Càmara Jordi, Ardanuy Carmen
Department of Microbiology, Hospital Universitari de Bellvitge - IDIBELL-UB, Barcelona, Spain.
Research Network for Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain.
Front Cell Infect Microbiol. 2025 Jul 18;15:1624521. doi: 10.3389/fcimb.2025.1624521. eCollection 2025.
The COVID-19 pandemic has impacted global health and altered respiratory pathogens. While SARS-CoV-2 vaccines have mitigated COVID-19 severity, emerging variants remain challenging. Co-infection of with respiratory viruses is associated with increased disease severity, but its relationship with SARS-CoV-2 remains unclear. This study aims to analyze their co-occurrence, focusing on disease progression, colonization rates and clinical outcomes.
To this end, three approaches were used. First, a laboratory-based analysis of invasive pneumococcal disease (IPD) in adults (2019-2023). Second, a retrospective analysis of COVID-19 clinical cases with pneumococcal isolates (March,2020-December,2023), including clinical and microbiological data such as patients' comorbidities, episode severity, serotypes and resistance genes. Third, a retrospective analysis to assess pneumococcal colonization in SARS-CoV-2 positive nasopharyngeal samples (May-October 2023; dual-target RT-PCR). WGS and bioinformatics were performed on both bacterial (serotyping and resistance analysis) and viral genomes (lineage determination). Statistical comparisons (Chi-square, Fisher's test), with significance set at <0.05.
First, IPD incidence declined during the COVID-19 pandemic, with cases dropping by 70% in both age groups (18-64 and >64) from 2019 to 2021 and rebounding after 2021, concomitant with the relaxation of non-pharmaceutical measures, especially among older adults. Pneumococcal serotype distribution remained stable with dominance of serotypes 3 and 8. Serotype 12F disappeared during the lockdown and re-emerged in 2023 as a multidrug-resistant sub-lineage through multi-fragment recombination, derived from the former GPSC26. Second, SARS-CoV-2 and pneumococcal co-infection occurred in 66 hospitalized patients, mainly by serotype 3 (15%), with resistance to macrolides (26.3%) and tetracycline (22.8%). Third, pneumococcal colonization in SARS-CoV-2-infected patients was low (2.8%), especially in older adults (>64 years; 1.5%), with slightly higher rates in severe cases (4.7% vs 2.5%; =0.404; IC95% 0.13-3.05) and young adults (4.8% vs 1.5%; =0.04; IC95% 0.92-15.21). Compared to colonized patients, those with co-infection had more comorbidities, more severe clinical presentations, higher hospitalization rates and lower vaccination rates.
This study highlights how non-pharmaceutical measures disrupt dynamics. Although pneumococcal colonization in SARS-CoV-2 patients appears to be infrequent, our data suggest an increase in disease severity. Then, vaccination programs and their monitoring remain critical in the prevention of respiratory infections.
新冠疫情影响了全球健康并改变了呼吸道病原体。虽然新冠病毒疫苗减轻了新冠病情的严重程度，但新出现的变种仍然具有挑战性。与呼吸道病毒的合并感染与疾病严重程度增加有关，但其与新冠病毒的关系仍不清楚。本研究旨在分析它们的共同出现情况，重点关注疾病进展、定植率和临床结果。
为此，采用了三种方法。首先，对成人侵袭性肺炎球菌疾病（IPD）进行基于实验室的分析（2019 - 2023年）。其次，对有肺炎球菌分离株的新冠临床病例进行回顾性分析（2020年3月 - 2023年12月），包括临床和微生物学数据，如患者的合并症、病情严重程度、血清型和耐药基因。第三，进行回顾性分析以评估新冠病毒阳性鼻咽样本中的肺炎球菌定植情况（2023年5月 - 10月；双靶点逆转录聚合酶链反应）。对细菌（血清分型和耐药性分析）和病毒基因组（谱系确定）都进行了全基因组测序（WGS）和生物信息学分析。进行了统计比较（卡方检验、费舍尔检验），显著性设定为<0.05。
首先，在新冠疫情期间IPD发病率下降，两个年龄组（18 - 64岁和>64岁）的病例数从2019年到2021年下降了70%，2021年后反弹，这与非药物措施的放宽同时发生，尤其是在老年人中。肺炎球菌血清型分布保持稳定，血清型3和8占主导地位。血清型12F在封锁期间消失，并于2023年作为多重耐药亚谱系通过多片段重组重新出现，源自前GPSC26。其次，66名住院患者发生了新冠病毒和肺炎球菌的合并感染，主要是血清型3（15%），对大环内酯类药物耐药（26.3%）和对四环素耐药（22.8%）。第三，新冠病毒感染患者中的肺炎球菌定植率较低（2.8%），尤其是老年人（>64岁；1.5%），重症病例中的定植率略高（4.7%对2.5%；P = 0.404；95%置信区间0.13 - 3.05），年轻人中的定植率为4.8%对1.5%；P = 0.04；95%置信区间0.92 - 15.21）。与定植患者相比，合并感染患者有更多合并症、更严重的临床表现、更高的住院率和更低的疫苗接种率。
本研究强调了非药物措施如何扰乱（病原体）动态变化。虽然新冠病毒患者中的肺炎球菌定植似乎不常见，但我们的数据表明疾病严重程度有所增加。因此，疫苗接种计划及其监测在预防呼吸道感染方面仍然至关重要。
