No abstract

To test our hypothesis that abnormal levels of endogenous carbon monoxide (CO) produced naturally by heme oxygenase-1 (HO-1) in response to infections of all kinds may be contributing to the morbidity and mortality associated with COVID-19, we searched PubMed for peer-reviewed literature on carbon monoxide and each of eleven abnormal blood tests, fourteen signs and symptoms, and five fatal complications of COVID-19 infection reported in a case series from a hospital in Wuhan, China: acute respiratory distress syndrome (ARDS), acute kidney injury, acute cardiac injury, arrhythmia, and shock. We found reports of acute exogenous CO poisoning causing all the same signs, symptoms and complications, and all the abnormal blood tests except D-dimer and procalcitonin. Our search also found endogenous HO-1 and CO levels correlated with these complications, independent of any inhaled CO exposure. In sharp contrast to the CO poisoning literature, most studies of endogenous CO interpret its close positive correlation with these acute conditions as protective, with some going so far as to recommend treating ARDS with inhaled CO. We conclude with new recommendations for testing endogenous CO poisoning in COVID-19 cases using devices approved by the US Food and Drug Administration that can distinguish CO coming from the lungs, arteries, veins, and average of all tissues, unlike current protocols for CO poisoning that only measure CO in arteries or veins but not both. Based on these findings, we appeal to clinicians to start testing CO levels in COVID-19 patients and to stop monitoring oxygen saturation with conventional pulse oximeters that overestimate oxygen saturation by the sum of carboxyhemoglobin and methemoglobin. We conclude by reviewing FDA-approved treatments that may help COVID-19 patients with endogenous CO poisoning. These include zinc-based drugs that lower the rate of endogenous CO production by inhibiting HO-1, and drug-free devices and methods that reduce the total body burden of CO after exogenous CO poisoning.

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by <3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4 ؉ cells, ranging from minor to eightfold for CD25 ؉ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.

The history of chemical sensitivity in America is reviewed from the first description published by Edgar Allan Poe in 1839, to its first medical definition as a symptom of neurasthenia in 1869, its rediscovery as allergic toxemia in 1945, its redefinition in 1987 as multiple chemical sensitivity (MCS), and its overlap in the 1990s with chronic fatigue syndrome, fibromyalgia syndrome, and Gulf War syndrome (GWS). More than half of the over 500 peer-reviewed articles on MCS support an organic basis for MCS, whereas less than one-quarter support a psychiatric basis. The same 2:1 difference is seen in the numbers of MCS researchers writing these articles and the number of journals publishing them. A psychogenic interpretation of MCS also is specifically rejected in the latest formal position statement on the subject, a 1994 consensus of the American Lung Association, American Medical Association (AMA), U.S. Environmental Protection Agency (US EPA), and U.S. Consumer Product Safety Commission (US CPSC) (U.S. Government Printing Office 1994–523–217/81322). This and other government recognition of MCS in policy, research, and scientific conferences are summarized. Dozens of federal, state, and local authorities accept MCS as a legitimate disease and/or disability that deserves reasonable accommodation in housing, employment, and public facilities. Official recognition is expected later in 1999 when the U.S. Centers for Disease Control and Prevention (CDC) announces a formal definition of MCS and the federal Interagency Workgroup on MCS releases its long-awaited final report, 4 years in the making. Given that epidemiological data from three states puts the prevalence of chemical sensitivity at 16 to 33% of the general population, 2 to 6% of whom have already been diagnosed with MCS, this truly is a hidden epidemic that deserves the priority attention of public health researchers and policy makers. Industrial toxicologists are encouraged to work on reducing and eliminating the use of synthetic fragrances, chemical sensitizers, and other irritants in consumer products and occupational settings.

No abstract