Introduction:
A cluster of atypical viral pneumonia cases was identified in Wuhan, China, in December 2019. A novel coronavirus has been identified as the cause, named later as Severe Acute Respiratory Syndrome -2 (SARS-CoV-2)[1, 2]. The World Health Organization (WHO) declared it a pandemic on 11 March 2020, with total confirmed cases exceeding 121 million cases worldwide and over 2.6 million deaths by 20th March 2021 [3]. Some people develop severe coronaviruses disease 2019 (COVID-19) disease while others remain asymptomatic or have a milder illness course [4]. Identifying predictors of poor outcomes is increasingly gaining importance to help to prioritize resources for high-risk patients and minimizing death. Older age and certain comorbid conditions like chronic renal, lung, and heart diseases are established predictors of worse prognosis in COVID-19 patients. In addition, hypoxemia, diarrhea, and high inflammatory markers like C- reactive protein (CRP) and interleukin-6 (IL-6) on admission are other predictors of worse prognosis [4-7].
In these patients, immune cells, namely lymphocytes, have been heavily implicated in controlling disease progression and clinical outcomes. Some studies have demonstrated that high leukocytes, specifically neutrophils [4, 7, 8], and T cell lymphopenia (CD3+, CD8+ [9, 10] and CD4) [11] are associated with increased mortality in patients admitted with COVID-19 pneumonia. Moreover, it was shown that older patients have lower counts and frequency of naïve (CD45RA+CCR7+CD27+CD28+) CD4+T cell contributing to the poor response of T cells [12]. These cells are required for the effective handling of new infections or vaccines [13, 14]. It has been already shown that hospitalized COVID-19 patients have reduced (CD45RA+CCR7+CD27+CD28+) CD4+ naïve subsets of T cells compared to healthy uninfected controls [15]. Furthermore, hospitalized patients with severe manifestations have a lower frequency of exhausted non-cytotoxic T cells (PD-1+ CD57-CD8+) [16].
Monocytes are other immune cells that are vital for normal and dysregulated immune response. Monocytopenia was found to be a predictor of worse outcomes in patients with severe community infections and sepsis [17]. Moreover, there is a reduction in the classic monocytes (CD14+CD16-) in severe COVID-19 infection and an increase in the inflammatory subsets (CD14+CD16+) [18]. Monocytes were also recently divided based on size into small and large subsets, coupled with a level of CD14 and CD16 expression into different subsets with different functional abilities[19].
Our study aimed to identify changes in immune variables, namely naïve CD4+ and CD8+, (CD45RA+CCR7+ CD27+CD28+), exhausted T cells CD8+ (PD-1+ CD57-), large and small inflammatory (CD14+CD16+) monocytes, and IL-6 level early in the course of COVID -19 infection as immunological predictors of poor outcomes including ICU admission and death.