The early 2020s began with ominous signs of a mysterious virus originating from China, spreading to the Western Hemisphere. Soon, the World Health Organization (WHO) and the Western nations including the United States (US) declared health emergencies [1]. The initial peak of the pandemic caused by the COVID-19 virus led to panic reminiscent of apocalyptic movie scenes. Accumulating dead bodies in big cities such as New York City could not be accommodated in the existing morgues and had to be preserved in refrigerated trucks. Some reread Albert Camu’s “Pest”, imagining numerous dead bodies scattered in an Algerian port city. In addition to tens of millions of children grieving from the loss of family members, relatives, and friends, 7.5 million became orphans worldwide, from January 1, 2020, through May 1, 2022 [2]. The toll was greater in the African continent and Southeast Asia than in the US, although the pandemic in America also gave rise to 150,000 orphans owing to the death of a parent or grandparent caregiver. Within the US, the mortality was greater among racial and ethnic minorities, in turn affecting those minority children more than others. Along with other contemporaneous social and political events in the US, the pandemic aggravated existing racism and xenophobia, especially against Asian Americans [3}. With the advancing digital culture, the pandemic accelerated societal disconnectedness and human isolation. The unknown cause and nature of the virus with relentless mutations and lack of treatment tools led to misinformation, politicization, and globalization of the infection. While the evidence for the benefit of vaccination has been accumulating including children, most of the world population does not have access and multiple segments of wealthy nations’ population have refused free vaccinations. According to the WHO’s epidemiological update from countries with available data on COVID-19, over 500,000 new cases and over 10,000 deaths were reported from 75 and 43 nations, respectively, during the last 28-day period from January 8 to February 4, 2024 [4]. However, the new cases significantly decreased to 147 000 in March 2025 [4]. The waning prevalence with increasing concerns about other serious viral infections such as mpox, H5N1 bird flu, measles and other acute respiratory viruses early 2025 has dulled the painful memories of COVID-19. While the acute crisis is over but still lingering, it would be important to look back and learn from the experiences and be better prepared for any future epidemic. The following are a brief summary of research findings beginning in early 2020 until 2024 with respect to biopsychosocial impacts of the COVID-19 pandemic on children and adolescents globally and of the US.