The SARS-CoV-2 pandemic is still ongoing. Previously, several studies have been conducted to investigate laboratory markers as a tool for severity assessment during COVID-19 infections. Biological markers such as Platelet count, D-dimer and IL-6, Lymphocytopenia and others have been used for assessment of severity in COVID-19 disease patients (infected by SARS-CoV-2 Alpha, Beta, Gamma, Delta, Epsilon, and other variants). We observed a significant drop in lymphocyte count among suspected SARS-CoV-2 clinical patients with symptoms of fever, running nose, breathing discomfort, cough, and others during Omicron and Centaurus variants spread in Pakistan. A multicenter, cross-sectional study was conducted from Jan 2021 to Aug 2022, on 118,561 subjects to evaluate hematological abnormalities among suspected patients. Of note, significantly decreased lymphocyte levels (lymphocytopenia) were observed among 43.05% of infected patients. Also, the levels of NA (39.03%), HGB (28.27%), MCV (22.62%), PLT (8.17%), and ALB (4.30%) were also reduced among infected patients. This suggests that lymphopenia can be used as an alternative, cost-effective, early diagnostic biomarker for clinical COVID-19 patients, even before the diagnosis via real-time PCR. In resource-limited countries, the current study is critical for policy-making strategic organizations for prioritizing lymphocytopenia-based screening (as an alternative, cost-effective diagnostic test) in clinical COVID-19 patients, before real-time PCR-based diagnosis.