Clinical and laboratory characteristics of patients hospitalized with severe COVID-19 in New Orleans, August 2020 to … – Nature.com

In this study we have characterized the demographic, clinical and laboratory aspects of COVID-19 among a population that experienced a disproportionate impact of the pandemic. Among the patients admitted with COVID-19, approximately 1 in 2 received supplemental oxygen, 1 in 3 received high-flow oxygen, and 1 in 10 died during their hospitalization. Our analysis is consistent with other reports of substantial early impact of COVID-19 in Louisiana. Together with evidence from other studies, our findings suggest that several factors may have been important in explaining the high case-severity in this cohort.

We found that patients with COVID-19 requiring high-flow oxygen were more likely to be older, which is consistent with other studies7. Nevertheless, approximately 66% of patients hospitalized with severe COVID-19 were younger than age 65, indicating that other factors were also important. Among all patients included in our analysis, 95% had underlying health conditions, and 80% had multiple comorbidities. Patients most frequently had cardiac disease, obesity, and diabetes mellitus, each of which are risk factors for severe outcomes from COVID-1912. Notably, we found that comorbidity was reflected in hospitalized cases, whether or not they received high-flow supplemental oxygen. Since we conditioned the analysis on hospital admission, comorbidity among non-severe cases might reflect an increased likelihood of admission, leading to potential collider bias20. A lower threshold for admission with underlying health conditions among patients without severe COVID-19 might explain why we did not find overall differences in underlying conditions by illness severity. Our finding that patients with more than two underlying conditions tended to be admitted more rapidly than other patients is suggestive of this. In view of these considerations, the lack of an overall difference in comorbidity by severity does not negate the importance of comorbidities in driving case-severity. Instead, the high prevalence of known risk factors suggests these factors were important drivers of adverse outcomes.

Among patients included in our analysis, 60.5% had Black non-Hispanic race and ethnicity. This proportion is slightly higher than that of inpatients documented to have COVID-19 in the participating hospitals (approximately 50%), and is similar to the proportion reported for New Orleans in the U.S. census (58%)21. Consistent with previous analyses, we did not find a difference in case-severity by race and ethnicity among hospitalized patients5,22. However, Black race was associated with an increased risk of hospitalization with COVID-19 in Louisiana after adjusting for comorbidity and socioeconomic status5, and this elevated risk might reflect an array of other factors, including those related to accessing care6.

Compared with non-severe hospitalized patients, we found that those requiring high-flow supplemental oxygen were more likely to be admitted greater than five days after symptom onset. This suggests that delayed access to healthcare might have contributed to adverse outcomes. In our analysis, patients received high-flow oxygen a median of 8days after symptom onset, and inpatient deaths occurred a median of 24days after illness onset. Severe COVID-19 typically progresses over 12weeks23, and patients who were admitted more than five days after illness onset were likely to have more severe illness by the time of presentation. We also found that patients with severe illness were more likely to have received treatment with remdesivir, dexamethasone, or other non-antiviral treatment (baricitinib or convalescent plasma). Since patients who met criteria for severe illness were likely to have been unwell at presentation, this is likely to reflect more treatment for patients presenting with more advanced disease, rather than any effect of treatment on severity; such an interpretation is supported by other evidence from other studies24.

Only 5% of hospitalized patients had completed a primary COVID-19 vaccine series during the period of analysis. This low proportion is likely to reflect both low vaccine coverage early in the pandemic, and an increased risk of COVID-19 if unvaccinated25. Similarly, approximately 20% of the U.S. population were estimated to have had prior infection during the period of analysis26. Since infection-induced immunity confers substantial protection against severe illness, patients admitted with COVID-19 would be expected to have a lower prevalence of prior infection during the period of analysis27. Although we did not have baseline serology results, low antibody titers during 07days is consistent with a low prevalence of prior infection in the cohort.

Our finding that 43% of patients did not have a positive anti-nucleocapsid result within 14days of illness onset is consistent with other evidence that it can take up to 14days or longer for new antibodies to develop28. Since a similar proportion of patients with severe and non-severe disease had evidence of seroconversion, we did not find evidence that severe disease reflected inadequate immune responses. However, our modeled estimates were limited by sparse data.

Among patients with available SARS-CoV-2 RT-PCR results, we found that severe COVID-19 was associated with a lower cycle threshold value in saliva specimens that were collected before any antiviral treatment was started. Cycle threshold values reflect the number of RT-PCR amplification cycles needed to detect viral RNA in a specimen, and are inversely related to the level of viral RNA; lower Ct values therefore imply the presence of higher RNA levels. Higher cycle threshold values over time are likely to reflect declining viral load after initial infection29,30. Lower cycle threshold values among patients with severe disease is broadly consistent with evidence of higher viral load in severe illness, after adjusting for other characteristics15,17,19. Detection of SARS-CoV-2 in saliva may reflect involvement of the oral cavity31. Previous studies have found similar detection of SARS-CoV-2 RNA in nasal and saliva specimens early after symptom onset32,33, although with differences in cycle threshold that may reflect differences in specimen collection33,34. Our findings were similar when restricted to patients with paired saliva and nasal specimens on the same day. However, data were sparse for paired specimens, and reasons for an association with saliva but not nasal specimens is unknown. Our findings of an association between case-severity and lower Ct value in saliva are consistent with those of others, who have reported that abundance of SARS-CoV-2 RNA in saliva was significantly higher in patients with risk factors for severe COVID-19, correlated with more severe COVID-19, and was superior to nasopharyngeal viral load as a predictor of mortality35. We did not find an association between lower cycle threshold and severity after treatment that might lower the viral load36,37, possibly because patients with severe illness were also more likely to received such medications, thereby masking differences in viral load.

Before considering implications of our analysis, several strengths and limitations need to be considered, in addition to those listed above. First, although we provided a detailed description of more than 500 patients with severe COVID-19, for some analyses we were limited by sparse data, resulting in wide confidence intervals. Second, our capture of potential confounding factors was incomplete, which might lead to residual or unmeasured confounding in multivariable analyses. Third, although we found a relatively high mortality among hospitalized patients, we may have underestimated deaths that occurred in the community or that did not meet our definition of severe illness. For example, two patients who died without meeting this definition might have had extrapulmonary manifestations of infection2. Fourth, for analysis purposes we used a relatively low threshold (6L/min) to determine severity based on oxygen level, limiting comparability with some other studies that have used 1015L/min as a threshold, and with guidelines that define severe illness based on oxygen saturation rather than supplemental flow38,39. Lastly, generalizability of our findings to other populations may be limited. Patients included in the analysis had similar overall demographic characteristics to other patients with COVID-19 in participating hospitals, but might have differed from patients admitted to other hospitals in the New Orleans area. Similarly, although overall patient characteristics were similar by availability of laboratory results, patients with laboratory data might be considered as a convenience sample within the main cohort. Overall, our scope was limited to analysis of patients who were hospitalized before widespread transmission of the Omicron SARS-CoV-2 variant and its subvariants.

Since predominance of the Omicron variant, average case-severity of SARS-CoV-2 infection has become milder3, both because of increased immunity from vaccination and infection40, and because of lower virulence compared with the Delta SARS-CoV-2 variant and ancestral variants13. Nevertheless, severe infections and deaths have continued to occur, both in individuals with and without clear risk factors. In our analysis, substantial comorbidity coupled with late presentation in an unvaccinated population are likely to have contributed to the high case-severity. Our study is relevant both in highlighting a patient population who experienced a disproportionate burden of COVID-19, and in describing severe COVID-19 in this group. Our findings of a correlation between severe illness and low cycle threshold in saliva may support the use of saliva PCR tests as a potential alternative to nasal PCR in the inpatient setting, though more work is needed to explore this association. To prepare for future epidemic and pandemic threats, our findings support broader efforts to address underlying inequalities and strengthen access to healthcare access and resilience of health systems6,41.

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Clinical and laboratory characteristics of patients hospitalized with severe COVID-19 in New Orleans, August 2020 to ... - Nature.com