Maciel Alex Bezerra Silva, Pinto Arlene Santos, Maia Silva Bernardo, Goulart Cassia Luz, Silva Luis Felipe Alho, Chaves Amanda Silva, Mouta Gabriel Santos, Sato Camila Miriam Suemi, Valente Jefferson, Mwangi Victor Irungu, de Melo Gisely Cardoso, Monteiro Wuelton, Lacerda Marcus, Arêas Guilherme Peixoto Tinoco, Sampaio Vanderson Souza, Costa Allyson Guimaraes, Almeida-Val Fernando
Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brazil.
Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado Do Amazonas, Manaus, AM, Brazil.
Front Immunol. 2024 Dec 23;15:1520193. doi: 10.3389/fimmu.2024.1520193. eCollection 2024.
In SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19.
I) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms.
This study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization.
Four months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual's recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; ). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years.
Although the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID.
在新型冠状病毒2型（SARS-CoV-2）感染中，细胞因子和实验室生物标志物在疾病进展中起关键作用，其长期水平与新冠后综合征（long COVID-19）的预后相关。
I）研究新冠疾病急性期和急性后期细胞因子、血液学和生化生物标志物的水平；II）评估新冠疫苗接种剂量对疲劳症状的影响。
本研究是一项探索性队列研究，嵌套于对有严重临床表现的疫苗接种前急性新冠感染幸存者的临床和实验室随访中。我们分析了50名新冠大流行前的SARS-CoV-2阴性健康对照、80名急性期（第1天、第7天和第14天）以及住院后4个月和2年期间患者的炎症生物标志物谱。
住院4个月后，91.3%（73/80）的患者出现新冠后症状，2年后仍有63.7%（51/80）的症状持续存在。将对照组细胞因子的基线值与随访时间进行比较，细胞因子白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-10（IL-10）在急性期较高，个体康复后随时间下降，而白细胞介素-1β（IL-1β）呈现相反变化，2年后仍保持较高水平。IL-1β、IL-10和肿瘤坏死因子（TNF）在急性感染后随时间增加，表明存在长期炎症反应。与接种三剂疫苗相比，接种四剂疫苗对男性人群的疲劳症状显示出轻微的保护作用（发病率比值比[IRR] 0.48，95%置信区间[CI] 0.22 - 1.02）。住院2年后中性粒细胞和白细胞计数显著降低。然而，血小板计数是最能反映长达2年新冠后症状预测的实验室生物标志物。
尽管急性疾病后新冠后症状的频率随时间下降，但出院2年后症状仍持续存在。接种第四剂加强针似乎对男性中与新冠后疲劳相关症状的减轻有显著影响。我们进一步确定了新冠后重要的实验室生物标志物。IL-1β、IL-10和TNF水平升高，以及IL-6、IL-18和IL-12p70水平降低，也为新冠后炎症状态提供了新的见解。
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