Table 2.
Pathogens detected among US patients with hepatitis of unknown etiology without significant underlying conditions from October 1, 2021 – September 30, 2022 (N=318).
| Characteristic | No. (%) |
|---|---|
| Patients | N=318* |
| Adenovirus positivity, no. positive/total no. tested (%) | |
| Any specimen type | 116/275 (42%) |
| Whole blood | 53/119 (45%) |
| Plasma | 22/85 (26%) |
| Serum | 8/17 (47%) |
| Any blood | 71/189 (38%) |
| Stool | 28/101 (28%) |
| Respiratory | 52/222 (23%) |
| Liver | 9/61 (15%) |
| SARS-CoV-2 | |
| Acute SARS-CoV-2 infection, no. positive/total no. tested (%) | 24/290 (8%) |
| History of SARS-CoV-2 infection† | 54/308 (18%) |
| Serology | 14/29 (48%) |
| Date of past infection, median (IQR) | Dec 21, 2021 (Aug 21, 2021–Jan 13, 2022) |
| Days since last infection, median (IQR) | 144 (92–230) |
| Gastrointestinal (GI) pathogens ‡ | 28/99 (28%) |
| Escherichia coli (EAEC, EPEC, ETEC, O157, EIEC) | 11/81 (14%) |
| Norovirus GI/GII | 4/84 (5%) |
| Rotavirus | 7/84 (8%) |
| Sapovirus | 6/81 (7%) |
| Salmonella § | 2/81 (3%) |
| Other GI pathogen# | 8/97 (8%) |
| Respiratory pathogens ‡ | 97/259 (37%) |
| Metapneumovirus | 13/235 (6%) |
| Rhinovirus/Enterovirus** | 73/252 (29%) |
| Human Coronavirus†† | 12/235 (5%) |
| Parainfluenza (1–4) | 9/235 (4%) |
| Influenza A‡‡ | 4/235 (2%) |
| RSV | 5/235 (2%) |
| Other respiratory pathogen§§ | 9/241 (4%) |
| Other viral testing | 45/212 (21%) |
| Acute EBV## | 18/87 (21%) |
| Acute CMV*** | 20/163 (12%) |
| HHV-6††† | 10/43 (23%) |
| Varicella-zoster virus††† | 1/13 (8%) |
| HSV-1††† | 1/54 (2%) |
| Hepatitis A – E‡‡‡ | 0/262 (0%) |
| Parvovirus B19 | 0/29 (0%) |
| Pathogen Count | |
| Median (range) | 1 (0, 12) |
| No Pathogen Detected | 100/304 (33%) |
| 1 pathogen | 116/304 (38%) |
| 2 pathogens | 45/304 (15%) |
| ≥3 pathogens | 43/304 (14%) |
Abbreviations: CMV=cytomegalovirus; EAEC= Enteroaggregative Escherichia coli (E. coli); EBV=Epstein-Barr Virus; EPEC= Enteropathogenic E. Coli; ETEC= Enterotoxigenic E. coli; EIEC= Enteroinvasive Escherichia coli; IQR= interquartile range; RSV=respiratory syncytial virus; HHV=human herpes virus.
This includes patients with no underlying medical conditions or underlying medical conditions unlikely to contribute to hepatitis (N=259), and patients with some underlying medical conditions that in the right circumstances, possibly could contribute and/or result in worsening hepatitis (N=59).
Based on 1) serology, 2) documentation of a positive SARS-CoV-2 PCR or antigen test more than 14 days prior to hepatitis onset, or 3) parental report of history of COVID-19 illness more than 14 days prior to hepatitis onset with a confirmed test result.
Most respiratory and GI pathogens tested as part of a panel but panel targets vary and panels used by clinical lab/facility also vary, thus the denominator of negative test results may be over-estimated.
Two patients positive by stool culture; 1 for s. enteriditis, 1 for unspecified salmonella spp
Eight patients positive for Campylobacter (2), C.difficile (3), Plesiomonas shigelloides (1), Vibrio nonsp. (1), Y.enterocolitica (1), Giardia (1), astrovirus (3)
Combines testing for rhinovirus/enterovirus via multiplex respiratory panel as well as testing via enterovirus specific NAAT (unknown specimen types).
Includes testing for the common HCVs (e.g. 229E, HKU1, HL63, OC43), not SARS-CoV-2
All influenza A serotype specific results combined (i.e., A/H3, A/H1N1, etc.)
Nine patients positive for parapertussis (1), pertussis (2), chlamydia pnuemoniae (1), mycoplasma (1), acinetobacter (1), klebsiella (1), p.aeruginosa (1), s.maltophilia (2), and unspecified respiratory pathogens (6)
Acute EBV defined as positive EBV viral capsid antigen (VCA) immunoglobulin M (IgM) or early antigen (EA) immunoglobulin G (IgG) test result, or diagnosis of primary EBV in the medical chart.
Acute CMV based on clinical diagnosis, verified by PCR IgM result.
HHV-6, Varicella-zoster virus, and HSV-1 defined as positive PCR or IgM; IgG antibody results were not included.
One patient with Hepatitis E IgM positive but IgG negative on initial and repeat testing, thus clinician expressed concern of false positive Hepatitis E results. Hepatitis virus testing using either antibody or RNA/DNA diagnostic tests were abstracted from the medical chart.