Initial SARS-CoV-2 viral load is associated with disease severity: a retrospective cohort study

Background: We aimed to assess the association between initial SARS-CoV-2 viral load and the subsequent hospital and intensive care unit (ICU) admission and overall survival. Methods: All persons with a positive SARS-CoV-2 RT-PCR result from a combined nasopharyngeal (NP) and oropharyngeal (OP) swab (first samples from unique persons only) that was collected between March 17, 2020, and March 31, 2021, in Public Health testing facilities in the region Kennemerland, province of North Holland, the Netherlands were included. Data on hospital (and ICU) admission were collected from the two large teaching hospitals in the region Kennemerland. Results: In total, 20,207 SARS-CoV-2 positive persons were included in this study, of whom 310 (1.5%) were hospitalized in a regional hospital within 30 days of their positive SARS-CoV-2 RT-PCR test. When persons were categorized in three SARS-CoV-2 viral load groups, the high viral load group (Cp < 25) was associated with an increased risk of hospitalization as compared to the low viral load group (Cp > 30) (ORadjusted [95%CI]: 1.57 [1.11-2.26], p-value=0.012), adjusted for age and sex. The same association was seen for ICU admission (ORadjusted [95%CI]: 7.06 [2.15-43.57], p-value=0.007). For a subset of 243 of the 310 hospitalized patients, the association of initial SARS-CoV-2 Cp-value with in-hospital mortality was analyzed. The initial SARS-CoV-2 Cp-value of the 17 patients who deceased in the hospital was significantly lower (indicating a higher viral load) compared to the 226 survivors: median Cp-value [IQR]: 22.7 [3.4] vs. 25.0 [5.2], OR[95%CI]: 0.81 [0.68-0.94], p-value = 0.010. Conclusions: Our data show that higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. We believe that our findings emphasize the added value of reporting SARS-CoV-2 viral load based on Cp-values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring.

Low Hepatitis C Viral Load Predicts Better Long-Term Outcomes in Patients Undergoing Resection of Hepatocellular Carcinoma Irrespective of Serologic Eradication of Hepatitis C Virus

Purpose Hepatitis C virus (HCV) infection has been recognized as a potent risk factor for the postoperative recurrence of hepatocellular carcinoma (HCC). However, little is known about the impact of HCV viral load on surgical outcomes. The study objective was to investigate clinical significance of HCV viral load on long-term outcomes of HCC. Patients and Methods Three hundred seventy patients who were classified as Child-Pugh class A and underwent curative liver resections for HCV-related HCC were divided into low and high viral load groups (≤ or > 5.3 log10IU/mL) based on the results of a minimum P value approach to predict moderate to severe activity of hepatitis; the clinical outcomes were then compared. Results The 5-year recurrence-free survival rate was 36.1% in the low viral load group and 12.4% in the high viral load group (P < .001). The 5-year overall survival rate was 76.6% in the low viral load group and 57.7% in the high viral load group (P < .001). Multivariate analysis confirmed significant correlation between high viral load and tumor recurrence with a hazard ratio of 1.87 (95% CI, 1.41 to 2.48; P < .001). Subanalysis revealed that the favorable results in the low viral load group were not attributed to whether or not serologic eradication of HCV was obtained both in primary and recurrent lesions. Conclusion Low HCV viral load predicts better long-term surgical outcomes in patients with HCC regardless of the serologic eradication of HCV.

Specificity of the Antibody Response to the Pneumococcal Polysaccharide and Conjugate Vaccines in Human Immunodeficiency Virus-Infected Adults

ABSTRACT Nonspecific antibodies, which are thought to be nonprotective, have been shown to contribute a substantial proportion of the measured concentration in the standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for pneumococcal polysaccharide capsular antibodies. The presence of such antibodies in human immunodeficiency virus (HIV)-infected persons has not been evaluated. The amount of nonspecific antibodies is proportional to the reduction in IgG antibody concentration that occurs with serum absorption with the heterologous polysaccharide 22F. We measured the amount of nonspecific antibodies before and after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4 counts of ≥200 cells/mm3. Blood was drawn before and 2 months after vaccination. For prevaccination sera, we found a substantial amount of nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured IgG concentration), but not for serotype 14. There tended to be proportionately less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but not for PPV. Subjects with a low HIV viral load (≤400 copies/ml) had proportionately more nonspecific antibodies than those with higher viral load before and after both vaccines. After 22F absorption, the geometric mean concentrations of antibodies were significantly higher post-PCV than post-PPV for the high viral load group for all five serotypes, but for no serotypes in the low viral load group. These findings confirm that absorption with a heterologous pneumococcal polysaccharide (e.g., 22F) is necessary to remove nonspecific antibodies in a standardized IgG ELISA for pneumococcal capsular antibodies in HIV-infected adults.