key: cord-1022380-sj9r1i1g
authors: Buitano, Bruno G; Morgenstern, Dan; Talavera, Juan; Zaldívar, Andrea; Martínez, Mercedes
title: 436. U-shaped-aggressiveness of SARS-CoV-2: Period Between Initial Symptoms and Clinical Progression to COVID-19 Suspicion. A Population-Based Cohort Study
date: 2021-12-04
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofab466.635
sha: adcbc2caecebe8ae5f56a9bf35c70a75bfcf9cbc
doc_id: 1022380
cord_uid: sj9r1i1g

BACKGROUND: Until now, studies have been focused on patient-centered risk factors, while SARS-CoV-2 aggressiveness has been established as causing 20% of severe and critical patients. However, there are still many unanswered questions concerning the clinical aggressiveness behavior of SARS-CoV-2. This study focuses on progression of symptoms as a marker of such aggressiveness, using the Period between initial symptoms and clinical progression to COVID-19 suspicion (PISYCS) to determine the risk of severe disease and mortality. METHODS: Historic cohort study of Mexican patients. Data from January-April 2020 were provided by the Health Ministry. Setting: Population-based. Patients registered in the Epidemiologic Surveillance System in Mexico. Participants were subjects who sought medical attention for clinical suspicion of COVID-19. All patients were subjected to RT-PCR testing for SARS-CoV-2. We measured the Period between initial symptoms and clinical progression to COVID-19 suspicion (PISYCS) and compared it to the primary outcomes (mortality and pneumonia) RESULTS: 65,500 patients were included. Reported fatalities and pneumonia were 2176 (3.32%), and 11568 (17.66%), respectively. According to the PISYCS, patients were distributed as follows: 14.89% in < 24 hours, 43.25% between 1–3 days, 31.87% between 4–7 days and 9.97% > 7 days. The distribution for mortality and pneumonia was 5.2% and 22.5% in < 24 hours, 2.5% and 14% between 1–3 days, 3.6% and 19.5% between 4–7 days, 4.1% and 20.6% > 7 days, respectively (p< 0.001). Adjusted-risk of mortality was (OR [95% CI], p-value): < 24 hours = 1.75 [1.55–1.98], p< 0.001; 1–3 days = 1 (reference value); 4–7 days = 1.53 [1.37–1.70], p< 0.001; > 7 days = 1.67 [1.44–1.94], p< 0.001. For pneumonia: < 24 hours = 1.49 [1.39–1.58], p< 0.001; 1–3 days = 1; 4–7 days = 1.48 [1.41–1.56], p< 0.001; > 7 days = 1.57 [1.46–1.69], p< 0.001. Risk of Mortality vs. PISYCS [Image: see text] Logistic regression anlaysis of mortality based on PISYCS. Note that risk of mortality is significantly higher when PISYCS is > 24 hours and < 7 days Risk of Pneumonia vs. PISYCS [Image: see text] Logistic regression anlaysis of developing pneumonia based on PISYCS. Note that risk of pneumonia is significantly higher when PISYCS is > 24 hours and < 7 days. CONCLUSION: The PISYCS shows a U-shaped SARS-CoV-2 aggressiveness pattern. Further studies are needed to corroborate the time-related pathophysiology behind these findings and possibly justify use of PISYCS as an initial evaluation tool and therapies/monitoring in high-risk patients. DISCLOSURES: All Authors: No reported disclosures

. Drop in symptomatic cases in nursing home (NH) residents with rise in COVID-19 vaccine coverage in the community, increase in personal protective equipment (PPE) adherence, or increase in coverage among NH residents.

In each panel, we plotted the mean number of cumulative symptomatic cases of COVID-19 in NH residents after 6 months since vaccine dose 2 (given 28 days after dose 1) and their 90% confidence interval (CI) for three healthcare personnel (HCP) coverage scenarios: 40%, 60%, or 80%. Coverage in HCP was independently modeled of community coverage. The top row is for NH resident coverage of 65%, the middle for 75%, and the bottom row for 85%. The columns (left to right) are for facility-level PPE adherence of 25% (low adherence), 50% (intermediate adherence), and 75% (high adherence). Weekly asymptomatic testing of HCP and twice-weekly outbreak testing in the facility were modeled with an assumed point-of-care test sensitivity of 80% (symptomatic persons) and 60% (asymptomatic persons) and with specificity of 100% and test turnaround time of 15 minutes. An outbreak is defined as an occurrence of 2 or more cases within 4 weeks of dose 2. Probability of no outbreak was calculated by counting how many simulations out of a total of 1000 simulations had ≤1 symptomatic case in NH residents or HCP within 4 weeks after dose 2 was administered in the nursing home. The first vaccine dose in residents and HCP was assumed to be given on day 1, and the second dose 28 days later. A probability value and its 90%-confidence interval (CI) at a given community and HCP coverage was calculated by pooling model outputs for 9 sets (3 PPE adherence values X 3 resident coverage levels) of model simulations. Simulations were performed assuming no asymptomatic testing or facility-wide outbreak testing.

Conclusion. Results suggest that increasing community vaccination coverage leads to fewer infections in NH residents. Testing asymptomatic residents and staff may have limited value when vaccination coverage is high. High adherence to recommended PPE may increase the likelihood that future COVID-19 outbreaks can be contained.

Disclosures. John A. Jernigan, MD, MS, Nothing to disclose

Examples of differentiating cytokine profiles by severity and time. Among SARS-CoV-2 PCR positive participants, IL-10 and IP-10 displayed increased levels in their acute plasma samples as clinical severity increased [A,C]. IL-10 and IP-10 also showed distinct time-dependent responses (ln(Cytokine level (pg/mL)) that differentiated the more severe from the less severe groups

Moderate and severe acute COVID-19 has a distinct cytokine profile from asymptomatic and mild cases, as detected from acute, subacute and convalescent plasma

Phenotypic Differences Between Distinct Immune Biomarker Clusters During the 'Hyperinflammatory' Middle-Phase of COVID-19

Joost Brandsma, PhD 2

PhD 2 ; 1 Uniformed Services University

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 , an infection with widely varying clinical severity. Severe COVID-19 was initially proposed to be secondary to cytokine storm syndrome (CSS). However, studies since showed that patients with severe COVID-19 rarely display CSS cytokine phenotypes, and may have more limited inflammatory responses instead.Methods. Prospective cohorts, aged 0-90 years of age who tested positive by polymerase chain reaction (PCR) for SARS-CoV-2 were enrolled from inpatient hospitals and outpatient testing centers in Memphis, TN from May 2020-January 2021. Longitudinal blood samples were obtained including acute, sub-acute and convalescent timepoints. Severity scores of asymptomatic, mild, moderate, and severe COVID-19 were assigned at time of convalescent assessment. Plasma was analyzed with a quantitative human magnetic 38-plex cytokine assay.Results. : 169 participants were enrolled, including 8 asymptomatic, 117 mild, 22 moderate and 17 severe cases, and 5 children with post-COVID-19 multisystem inflammatory syndrome in children (MIS-C). All moderate and severe patients were hospitalized and received treatment (39%). Clear distinctions were seen between asymptomatic-mild cases and moderate-severe cases at acute timepoints and during disease progression for GCSF, IL-8, IL-10, IL-15, IL-1Ra, IP-10, MIP-1a, MIP-1β, and TGFα. There was a significant difference between participants who did and did not require hospitalization for acute timepoint levels of IL-10, IL-15, MIP-1 β and TGFα (p< 0.01). Only 4 participants with active COVID-19 were found to meet criteria for CSS (2%), only 3 of which were severe. MIS-C participants showed nearly universally elevated cytokine levels compared to those with active COVID-19.Temporal and severity associations of IL-10 and IP-10