Using rhesus macaques infected with SARS-CoV-2, researchers have observed that acute heart remodelling and fibrosis as an effect of COVID-19 occurs in association with systemically elevated inflammatory cytokines and is not characterised by direct virus infection of heart tissue or cardiac immune infiltration.

Mr Michael Sayegh (Emory University, USA) presented the findings [1]. Myocardial injury is common in COVID-19 patients, affecting up to 20% of patients [2]. Understanding the aetiology of myocardial injury in COVID-19 in humans has been hampered because of the unavailability of tissue. The researchers, therefore, decided to study the effect of SARS-CoV-2 infection on the heart using rhesus macaques, which share 91% homology to the human ACE2 receptor. In total, 4 animals were inoculated with SARS -CoV-2 intratracheally and intranasally in the experimental arm, and 5 animals formed the control arm. Blood was taken 4 days prior to inoculation for baseline levels. Further blood samples were collected 4, 7, and 10 days post-infection. On day 10, heart tissue was harvested for histological and cellular analyses.

In human post-mortem heart tissue, COVID-19 patients (n=5) had significantly higher areas of fibrotic tissue staining for trichrome compared with age-matched corpses of individuals who had not died of COVID-19 (n=8; P=0.024099). Similarly, in the rhesus macaque model, the animals in the experimental arm showed significantly more cardiac fibrosis than non-infected controls (P=0.0988).

To determine whether the observed fibrosis was attributable to direct infection of the heart, researchers analysed the necropsy samples. There was no virus detected in cardiac tissue 10 days post-inoculation. To look at immune presence in the heart, the researchers isolated white blood cells from 2 g of each heart.  Very few cardiac white blood cells could be detected, and further analysis indicated that they were not activated or associated with an inflammatory profile. Immunofluorescence experiments confirmed that there was low or no direct immune infiltration of the heart by the virus.

However, looking at systemic inflammation markers, most appeared to peak at 4-5 days post-inoculation, including C-reactive protein, ferritin, and fibrinogen. ELISA arrays of necropsy cardiac left ventricular tissue indicated that most inflammatory cytokines were elevated compared with the control animals.

In conclusion, although there was no evidence of direct viral infection of the heart by SARS-CoV-2, and no evident immune cell infiltration into the heart, the researchers observed significant cardiac fibrosis, consistent with human observational studies. The researchers noted that the diseased animals had elevated systemic inflammatory markers that associate with the onset of myocardial injury.  The clinical implication is that ameliorating systemic inflammation should alleviate COVID-19-associated myocardial injury, but this warrants further research.

  1. Sayegh M. et al. Systemic Inflammation in Acute SARS-CoV-2 Infection May Lead to Elevated Cardiac Cytokines and Adverse Remodeling. Late-Breaking Basic Science 1 session. Virtual AHA Scientific Sessions 2020, 13-17 Nov.
  2. Shi S, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020 Jul 1;5(7):802-810.