Medical Research Council: Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
mBio. 2021 Jan 8;12(1):e02347-20. doi: 10.1128/mBio.02347-20.
In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes. SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.
2019 年 12 月,一种新型冠状病毒(CoV)作为人类病原体出现,即 SARS-CoV-2。关于人类冠状病毒感染,在 HIV 感染者中数据较少。在这项研究中,我们探究了肺炎住院的 HIV 感染者和非感染者中肺炎链球菌( pneumococcal )合并季节性 CoV 感染的作用。我们还描述了这些感染的流行率和临床表现。共有 39836 名儿童参加了一项关于 9 价肺炎球菌结合疫苗(PCV9)有效性的随机、双盲、安慰剂对照临床试验,随访至 2 岁时发生下呼吸道感染住院情况。在住院时采集鼻咽抽吸物,并通过 PCR 筛查四种季节性 CoV。HIV 感染者中 CoV 相关肺炎的发生率(19.9%)高于非 HIV 感染者(7.6%,<0.001)。在 HIV 感染者中检测到连续的 CoV 感染。HIV 感染者中 CoV 相关肺炎的病死率(30.4%)高于非 HIV 感染者(2.9%,=0.001)。在 HIV 感染者中,有 36.8%(≥40mg/L)和 64.7%(≥0.5ng/ml)的病例 C-反应蛋白和降钙素水平升高。在非 HIV 感染者中,PCV9 组与安慰剂组相比,CoV 相关肺炎住院率降低 64.0%(95%CI:22.9%至 83.2%)。这些数据表明,感染可能在地方性 CoV 相关肺炎的发展中起作用,PCV 可能预防儿科 CoV 相关住院,而感染 CoV 的 HIV 感染者发生更严重的结局。SARS-CoV-2 可能导致严重住院,但除了观察到高水平的炎症标志物外,例如与细菌感染相关的降钙素,对于这些严重病例中继发性细菌感染的作用知之甚少。我们对 PCV 的一项双盲随机试验进行了二次分析,以检查其在大流行之前对人类 CoV 感染的影响。我们发现,接受 PCV 治疗的 HIV 感染者和非感染者均因季节性 CoV 导致的住院率降低,这表明肺炎链球菌合并感染可能在严重住院 CoV 感染中起作用。