By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Seasonal coronaviruses, which are a frequent cause of benign upper respiratory tract infections, may be fatal in severely immunocompromised patients.

SOURCE: Piñana JL, Xhaard A, Tridello G, et al; Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation and Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH). Seasonal human coronaviruses respiratory tract infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis 2020; Aug. 29. doi: 10.1093/infdis/jiaa553. [Online ahead of print].

Piñana and colleagues, representing the European Society for Blood and Marrow Transplantation and the Spanish Hematopoietic Stem Cell Transplantation (HCT) and Cell Therapy Group, retrospectively examined the records of 402 allogeneic HCT patients with 449 seasonal human coronavirus (HCoV) infections over a seven-year period ending in January 2019. The patients, whose mean age was 46 years (range, 0.3-73.8 years), had been seen at 31 transplant centers in 13 countries in Asia, Australia, and South America. Because they received their grafts from unrelated adult donors, cord blood, or haplo-identical family donors, 57% were considered high risk.

A single HCoV I 229E 92250 infection occurred in 364 (90.4%) patients, while 38 (9.5%) had two or more episodes. All four viral subtypes were encountered, with OC43 accounting for 38% of episodes, followed by 229E (22%), NL63 (14%), and KHU1 (12%). Non-sub-typable HCoV were found in 17.5% and more than one HCoV subtype was detected in 15 (3%) of 434 episodes. Infections first occurred from nine days before transplantation (i.e., during conditioning) to 20 years after.

Infection of the lower respiratory tract, as defined by the presence of a pulmonary infiltrate in imaging, occurred in 121 (27%) patients. Only approximately one-third had fever at the time of diagnosis, and only 18% were hospitalized. Sixty-two percent received empiric antibiotics, 21.1% received intravenous immune globulin (IVIG), and 12.7% required oxygen support. Only 13 (2.9%) required intensive care.

The overall mortality rate was 7%, but it was 16.7% in those people with lower respiratory tract infection in whom the associated risk factors were an absolute lymphocyte count < 0.1 × 109/mL, corticosteroid use, and intensive care unit admission. Among those with lower respiratory infections, 24% had bacterial coinfection, while 41% had coinfection with another community-acquired respiratory virus.

COMMENTARY

The seasonal coronaviruses (NL63, OC43, KHU1, and 229E) are a common cause of upper respiratory tract infections, including the common cold, with most cases occurring in the winter months and overlapping with the influenza season. Although infection in the general population generally is not severe, accumulating evidence suggests that this may not be true of some vulnerable populations. In fact, a mortality rate as high as 8% has been seen in outbreaks in elderly residents of long-term care facilities.1

The mortality rate in patients with lower respiratory infection reported by Piñana and colleagues was 16.7%. In contrast, a much higher mortality rate has been reported in HCT and hematologic malignancy patients whose lower tract localization was proven by virus detection in bronchoalveolar lavage fluid (BAL).2 Ogimi and colleagues in Seattle reviewed 37 episodes in 35 patients with such positive BAL specimens, 21 (60%) of whom required oxygen therapy at the time of diagnosis, with 19 (54%) dying within 90 days. While coinfections (including ones due to viruses, fungi, and bacteria) were detected in 57% of episodes, mortality rates did not significantly differ between those with and without coinfection. In an adjusted comparison with cases of lower respiratory tract infection in a similar patient population, mortality was similar to that observed with infections due to respiratory syncytial virus, influenza, and parainfluenza virus — each of which is recognized as a significant cause of morbidity and mortality in immunocompromised patients.

There is no known effective therapy for coronavirus infections. Of note, however, is that remdesivir, which currently is considered a standard of care for treatment of patients with COVID-19 (caused by the coronavirus SARS-CoV-2) is active in vitro against at least three of the seasonal coronaviruses.3,4

REFERENCES

  1. Patrick DM, Petric M, Skowronski DM, et al. An outbreak of human coronavirus OC43 infection and serological cross-reactivity with SARS coronavirus. Can J Infect Dis Med Microbiol 2006;17:330-336.
  2. Ogimi C, Waghmare AA, Kuypers JM, et al. Clinical significance of human coronavirus in bronchoalveolar lavage samples from hematopoietic cell transplant recipients and patients with hematologic malignancies. Clin Infect Dis 2017;64:1532-1539. [Published correction appears in Clin Infect Dis 2017;65:1431-1433].
  3. Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med 2020;12:eabb5883.
  4. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017;9:eaal3653.