Inflammatory Biomarkers Differ among Hospitalized Veterans Infected with Alpha, Delta, and Omicron SARS-CoV-2 Variants

Abstract

Mortality due to COVID-19 has been correlated with laboratory markers of inflammation, such as C-reactive protein (CRP). The lower mortality during Omicron variant infections could be explained by variant-specific immune responses or host factors, such as vaccination status. We hypothesized that infections due to Omicron variant cause less inflammation compared to Alpha and Delta, correlating with lower mortality. This was a retrospective cohort study of veterans hospitalized for COVID-19 at the Veterans Health Administration. We compared inflammatory markers among patients hospitalized during Omicron infection with those of Alpha and Delta. We reported the adjusted odds ratio (aOR) of the first laboratory results during hospitalization and in-hospital mortality, stratified by vaccination status. Of 2,075,564 Veterans tested for COVID-19, 29,075 Veterans met the criteria: Alpha (45.1%), Delta (23.9%), Omicron (31.0%). Odds of abnormal CRP in Delta (aOR = 1.85, 95% CI:1.64–2.09) and Alpha (aOR = 1.94, 95% CI:1.75–2.15) were significantly higher compared to Omicron. The same trend was observed for Ferritin, Alanine aminotransferase, Aspartate aminotransferase, Lactate dehydrogenase, and Albumin. The mortality in Delta (aOR = 1.92, 95% CI:1.73–2.12) and Alpha (aOR = 1.68, 95% CI:1.47–1.91) were higher than Omicron. The results remained significant after stratifying the outcomes based on vaccination status. Veterans infected with Omicron showed milder inflammatory responses and lower mortality than other variants.

Relationship between the Viral Load in Patients with Different COVID-19 Severities and SARS-CoV-2 Variants

“…However, unlike our results, Tsukagoshi and collaborators [ 30 ] found that the viral load in deceased patients was significantly higher; although, we must consider that in their study, the sample was composed of only 286 individuals. Similarly, Liu et al also concluded that patients with severe COVID-19 tend to have a high viral load and a long virus shedding period [ 31 ].…”

“…Garay and collaborators [31] estimated the association of bacterial pneumonia with the mortality of patients due to COVID-19 and found that 89 of 252 patients tested positive for bacteria that cause pneumonia, which increased the percentage of deaths and could explain why hospitalized patients may have a low viral load but greater severity due to secondary infection. However, unlike our results, Tsukagoshi and collaborators [30] found that the viral load in deceased patients was significantly higher; although, we must consider that in their study, the sample was composed of only 286 individuals. Similarly, Liu et al also concluded that patients with severe COVID-19 tend to have a high viral load and a long virus shedding period [31].…”

“…Also, in a study that compared inflammatory markers among patients hospitalized during Omicron infection with those of Alpha and Delta, showed that levels of CRP in Delta and Alpha were significantly higher compared to Omicron; the same trend was observed for ferritin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and albumin. So, in accordance with our results, the mortality in Delta and Alpha was higher than Omicron [30].…”

Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes’ Structure

“…Interestingly, these findings were confirmed in a subsequent study published by Barh et al [39], who reported that pro-inflammatory cytokines production (especially interleukin 6) is decreased in patients infected with the Omicron variant compared to those infected by the Delta variant. In keeping with these findings, Park et al studied nearly 30,000 veterans with Alpha, Delta, and Omicron infections [40] and observed that the risk of having enhanced levels of C reactive protein was higher in those infected by Delta (odds ratio [oR], 2.30; 95%CI, 2.18-2.4) or Alpha (OR, 2.29; 95%CI, 2.14-2.45) compared to Omicron. A similar trend was seen by measuring ferritin (i.e., another well-known inflammatory biomarker), in that the likelihood of having increased concentrations of this protein was higher in COVID-19 patients infected by Delta (OR, 1.91; 95%CI, 1.81-2.02) or Alpha (OR, 1.54; 95%CI, 1.45-1.65) compared to Omicron.…”

Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes Structure

“…Interestingly, these findings were confirmed in a subsequent study published by Barh et al [41], who reported that pro-inflammatory cytokines production (especially interleukin 6) is decreased in patients infected with the Omicron compared to those infected by Delta variant. In keeping with these findings, Park et al studied nearly 30000 veterans with Alpha, Delta and Omicron infections [42] and observed that the risk of having enhanced levels of C Reactive protein was higher in those infected by Delta (Odds Ratio [OR], 2.30; 95%CI, 2.18-2.4) or Alpha (OR, 2.29; 95%CI, 2.14-2.45) compared to Omicron. A similar trend was seen by measuring ferritin (i.e., another well-known inflammatory biomarker), in that the likelihood of having increased concentrations of this protein was higher in COVID-19 patients infected by Delta (OR, 1.91; 95%CI, 1.81-2.02) or Alpha (OR, 1.54; 95%CI, 1.45-1.65) compared to Omicron.…”