The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score

We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.

Prevalence and impact of COVID-19 sequelae on treatment pathways and survival of cancer patients who recovered from SARS-Cov-2 infection

Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment.

Prevalence and clinical impact of asymptomatic or mildly symptomatic sarscov-2 infection among actively treated cancer patients during recent covid-19 pandemic peak in Italy

Background: The European SARS-CoV-2 pandemic had its first epicentre in Italy, particularly in the area of Bergamo. In spite of a significant mortality rate, in the majority of cases the spectrum of Covid-19 ranges from asymptomatic to mildly symptomatic infection. No information is available on the prevalence and clinical impact of asymptomatic or mildly symptomatic SARSCoV-2 infection among actively treated cancer patients during pandemic. Patients and methods: From April 1st, 2020 to the end of the month, 560 consecutive and unselected patients, scheduled for anticancer treatment at our facility and without clinical suspicious of Covid-19, were evaluated and tested for SARSCoV-2. We implemented a two-step diagnostics, including a rapid serological immunoassay for anti-SARSCoV-2 IgG/IgM and a pharyngeal swab RT-PCR assay in case of IgM seropositivity. Results: In 560 patients, 172 (31%) resulted positive for SARSCoV-2 IgM/IgG antibodies, regardless of type of cancer, stage and treatment. All IgM-seropositives were then tested with RT-PCR pharyngeal swabs and 55/146 (38%) proved to be SARSCoV-2 carriers, with slightly difference between mildly symptomatic vs. asymptomatic patients (38 vs. 17). Therefore, the two-step procedure allowed the identification of 55 (10%) silent carriers in the whole study population and magnified the number needed to test (NNT) with the pharyngeal swab RT-PCR assay to detect a silent virus carrier (NNT: 2.6 vs. 10, with or without serological selection). At a very early follow up (8 wks), in 114 SARSCoV-2-seropostive/RT-PCR-negative patients, who continued their anticancer therapies, none but one developed a symptomatic Covid-19 illness. Conclusions: Among cancer patients, the two-step diagnostics strategy with serology followed by pharyngeal swab for asymptomatic or mildly symptomatic SARSCoV-2 infection is feasible and effective and can help selecting cancer patients on treatment who might be silent carriers of the virus. The early safety outcome of patients previously exposed to SARSCoV-2 supports the recommendation to continue active treatment, at least in the case of negative RT-PCR test.

Prevalence and clinical impact of asymptomatic or mildly symptomatic SARSCoV-2 infection among actively treated cancer patients during COVID-19 pandemic in Italy

Background: The European SARS-CoV-2 pandemic had its first epicentre in Italy, particularly in the area of Bergamo. In spite of a significant mortality rate, in the majority of cases the spectrum of COVID-19 ranges from asymptomatic to mildly symptomatic infection. No information is available on the prevalence and clinical impact of asymptomatic or mildly symptomatic SARS-CoV-2 infection among actively treated cancer patients during pandemic. Methods: From April 1st, 2020 to the end of the month, 560 consecutive and unselected patients, scheduled for anticancer treatment at our facility and without clinical suspicious of COVID-19, were evaluated and tested for SARS-CoV-2. We implemented a two-step diagnostics, including a rapid serological immunoassay for anti-SARS-CoV-2 IgG/IgM and a pharyngeal swab RT-PCR assay in case of IgM seropositivity. Results: In 560 patients, 172 (31%) resulted positive for SARS-CoV-2 IgM/IgG antibodies, regardless of type of cancer, stage and treatment. All IgM-seropositives were then tested with RT-PCR pharyngeal swabs and 55/146 (38%) proved to be SARS-CoV-2 carriers, with slightly difference b/w mildly symptomatic vs. asymptomatic patients (38 vs. 17). Therefore, the two-step procedure allowed the identification of 55 (10%) silent carriers in the whole study population and magnified the number needed to test (NNT) with the pharyngeal swab RT-PCR assay to detect a silent virus carrier (NNT: 2.6 vs. 10, with or without serological selection). At a very early follow up (8 wks), in 114 SARS-CoV-2-seropostive/RT-PCR-negative patients, who continued their anticancer therapies, none but one developed a symptomatic COVID-19 illness. Conclusions: Among cancer patients, the two-step diagnostics strategy with serology followed by pharyngeal swab for asymptomatic or mildly symptomatic SARS-CoV-2 infection is feasible and effective and can help selecting cancer patients on treatment who might be silent carriers of the virus. The early safety outcome of patients previously exposed to SARS-CoV-2 supports the recommendation to continue active treatment, at least in the case of negative RT-PCR test. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.