COVID-19 Infection Rates in the US Fall Short of Reaching Herd Immunity

Illustration of antibodies (y-shaped) responding to a coronavirus infection. Different strains of coronavirus are responsible for diseases such as the common cold, gastroenteritis and SARS (severe acute respiratory syndrome). The new coronavirus SARS-CoV-2 (previously 2019-CoV) emerged in Wuhan, China, in December 2019. The virus causes a mild respiratory illness (Covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells’ machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by phagocyte immune cells.
Study authors evaluated the incidence of VTE and major bleeding in critically ill patients with COVID19, and examined the observational effect of early therapeutic anticoagulation on survival.

Patients had similar in-hospital survival regardless of early initiation of therapeutic anticoagulation in the first 2 days of intensive care unit (ICU) admission, according to findings published in Annals of Internal Medicine.

Using data from the national multi-center cohort study titled Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), study authors evaluated the incidence of venous thromboembolism (VTE) and major bleeding, and identified VTE risk factors in critically ill COVID-19 patients.

Between March 4 and April 11, 2020, investigators included 3239 COVID-19 patients admitted to the ICU at 67 hospitals nationwide. Study authors designed a target trial emulation (n=2809) to examine the observational effect of therapeutic anticoagulation in the first 2 days of ICU admission on in-hospital survival. In this primary analysis, survival time was defined as the interval from ICU admission to death, censored at hospital discharge, or at the end of follow-up, whichever occurred first.

During the first 14 days of ICU admission, study authors identified 204 patients (6.3%) with radiographically confirmed VTE and 90 patients (2.8%) with major bleeding. By day 28, 78 patients with VTE (38.2%) and 56 patients with major bleeding (62.2%) died. Researchers identified male sex (OR, 1.60; 95% CI, 1.13-2.27) and higher D-dimer concentration upon ICU admission (OR, 1.79; 95% CI, 1.14-2.81) to be independently associated with a higher risk for VTE.

In the target trial emulation, investigators used inverse probability weighting to adjust for confounding when analyzing the effect of early anticoagulation initiation on in-hospital survival. After applying the weighting, the primary analysis showed similar survival rates between patients with early anticoagulation and those without (hazards ratio, 1.12; 95% CI, 0.92-1.35).

According to the observed results, data suggests that VTE incidence rates in critically ill COVID-19 patients may be lower in the United States compared to other countries, thus the early initiation of therapeutic anticoagulation may not have a survival benefit. It was noted to properly identify patients that may benefit from early therapeutic anticoagulation in the absence of standard indications due to the high mortality in those with major bleeding. Additionally, based on the trial emulation, anticoagulation therapy may have reduced VTE risk at the expense of increased major bleeding risk.

Limitations of this study include the following:

  • Inability to exclude all possible residual confounding as this study was an observational analysis
  • Incidence underestimation of VTE and major bleeding as data used were limited within the first 14 days after ICU admission

“It is tempting to speculate that early, empirical therapeutic anticoagulation could be beneficial in select patients, such as men with elevated D-dimer on ICU admission. However, in our target trial emulation, we found no benefit of early therapeutic anticoagulation overall or in any subgroup,” the study authors concluded, noting that further clinical research is needed for therapeutic anticoagulation in critically ill COVID-19 patients.


Al-Samkari H, Gupta S, Leaf RK, et al; for the STOP-COVID Investigators. Thrombosis, bleeding, and the observational effect of early therapeutic anticoagulation on survival in critically ill patients with COVID-19. Ann Intern Med. Published online January 26, 2021. doi:10.7326/M20-6739.