Clinical and Economic Impact of COVID-19 and Serologic Protection among Farm Workers: Results from the Guatemala Agricultural Workers and Respiratory Illness Impact (AGRI) Study

Background. In the Guatemala AGricultural workers and Respiratory Impact (AGRI) study, we evaluated the clinical and socioeconomic burdens of respiratory disease in a cohort of Guatemalan banana farm workers. Methods. All eligible workers were offered enrollment from June 15-December 30, 2020, and annually, then followed for influenza-like illnesses (ILI) through: 1) selfreporting to study nurses, 2) sentinel surveillance at health posts, and 3) absenteeism. Workers with ILI submitted nasopharyngeal swabs for influenza, RSV, and SARS-CoV-2 testing, then completed surveys at days 0, 7, and 28. Enrollment and acute-illness serum samples were tested for anti-SARS-CoV-2 nucleocapsid IgG (anti-N, Roche Elecsys ), and neutralizing antibodies (NAb) were tested in a subset using a lentivirus-based pseudovirion assay. Results. Through October 10, 2021, 1,833 workers were enrolled. The majority were male (84%), young (mean 31 years), and healthy (< 13% had comorbidity). Through October 10, 2021, 1,833 workers developed 169 ILIs (12.0/100 person-years) and 43 (25.4%) of these ILIs were laboratory-confirmed SARS-CoV-2 (3.1/100 person-years). Workers with SARS-CoV-2-positive ILI reported more anosmia (p< 0.01), dysgeusia (p< 0.01), difficulty concentrating (p=0.01), and irritability (p=0.01), and greater clinical and well-being severity scores (Flu-iiQ) than testnegative ILIs (Fig 1);they also had greater absenteeism (p< 0.01) and lost income (median US$127.1, p< 0.01). Among 1334 workers enrolled in 2020, 616 (46.2%) had anti-N IgG suggestive of prior SARS-CoV-2 infection. COVID-19 incidence density for IgG-seropositive workers was 0.4/100 Person Years (PY), lower than those who were seronegative (2.3/100 PY) (Fig 2). At enrollment, anti-N IgG titers in serum correlated with neutralizing antibody titers (R2 =0.26, p< 0.0001). Notably, in < 6 months from enrollment, most workers with follow-up NAb testing (65/77, 84%) exhibited a 95% decrease in neutralizing antibody titers. Conclusion. Guatemalan farm workers suffered a significant burden of COVID-19, including more severe clinical and economic outcomes than other respiratory illnesses. Ongoing vaccination programs and longitudinal serology will provide additional insight into long-term immunity.

Predictive comorbidities of hospital admission in 1,571 SARS- CoV-2 positive patients: analysis of administrative data from an Italian Local Health Autority.

Purpose: Globally, age and some comorbidities have been associ-ated with the risk of more severe outcomes of COVID-19. The purpose of this research is to calculate the hospitalization rate of SARS-CoV-2 positive patients in an Italian Local health Authority (LHA) and to examine whether medical comorbidities encoded through pharmaceutical administrative data are predictors of hospital admission in patients with a positive SARS-CoV-2 naso-pharyngeal swab. Methods: This retrospective observational study was conducted in a LHA of Pescara. Comorbidities were coded through the consumption of drugs, using the WHO's Anatomical Therapeutic Chemical (ATC) classification System. The admission was ascertained by checking the hospital discharge records where generated. Results: During the study period, 1571 patients were tested positive for SARS-CoV-2 oro-and-nasopharyngeal swab. Multivariable logistic analisys showed as predictors of admission an age ≥65 in the total sample (aOR 10.91; 95%CI 6.86-17.36) as well as in the male (aOR 12.64;95%CI 6.42-24.87) and female. (aOR 9.27; 95%CI 4.87-17.66) in SARS-CoV-2 positive patients. Comorbidities assiociated with admission were (GERD) in overall (AdjOR 1.58; 95% CI 1.06-2.34) and male (AdjOR 2.30; 95%CI 1.12-4.72) samples and anticoagulants drugs use in male (AdjOR 3.90; 95% 1.11-13.65) sample, the presence of congestive heart failure (CHF) in female (AdjOR 0.47;95%CI 0.27-0.83) sample results as protective factor. Conclusion: In conclusion, increasing age, male gender and PPI use are positively associated while female gender and CHF-related drug use are negatively associated with hospitalization in SARS-CoV-2 positive patients.

Anemia and iron metabolism in patients with sars-cov-2 infection: The role of inflammation and hypoxia

Background: Coronavirus Disease (COVID-19) could be considered as a human model of marked inflammation combined with severe hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction. In patients with SARS-CoV-2 infection, Hb levels tend to be relatively high even in the context of severe disease and marked inflammation. A better understanding of erythropoiesis and iron metabolism in COVID-19 could contribute to elucidate the relationship between hypoxia and inflammation on erythropoietic control. Aims: To investigate the prevalence of anemia, the alterations of iron homeostasis,and the relationship between inflammation,hypoxia and erythropoiesis in a cohort of COVID-19 patients admitted both to medical wards and intensive care unit (ICU). Methods: We retrospectively analyzed data of 303 patients with COVID- 19 (178 subjects admitted to medical wards and 125 subjects admitted to the ICU). Biochemical parameters were collected on admission (T0), after 7 days of hospitalization (T1) and at discharge/death (T2). Results: The median age of the patients was 62 years (53-71) and 72% were males. ICU patients had lower mean Hb levels compared to non- ICU patients (11.3±1.8 vs 12.8±1.8 g/dL at T0, 10.2±1.6 vs 12.2±1.9 g/ dL at T1, 10±1.4 vs 12±1.7 g/dL at T2;p<0.001). Mean Hb concentration did not fall under 12 g/dl in the non-ICU group and under 10 g/ dl in the ICU group during hospitalization. Hb decreased by approximately 1 g/dl in both cohorts during the first 7 days of hospitalization, then remained stable until discharge. ICU patients also showed increased inflammatory markers and ferritin levels (1401 vs 839 mcg/l at T0, p<0.001;913 vs 832 mcg/L at T1, p ns;764 vs 651 mcg/L at T2, p ns). There were no significant differences in other iron parameters between groups. Hypoxia was a prominent feature of ICU patients (P/F ratio 91 vs 224, p<0.001). Patients who were anemic on admission maintained relatively constant Hb concentrations from T0 to T2 (10.8 g/dL at T0, 10.2 g/dL at T1 and 10.4 g/dL at T2), thus remaining in a range of mild to moderate anemia. Conversely, the non-anemic group displayed a greater reduction of Hb levels (13.7 g/dl at T0, 12.7 g/dl at T1, 12 g/dl at T2). Anemic subjects were more hypoxic than non-anemic patients (P/F 151 vs 292 at T0, p<0.001) and showed significantly higher levels of CRP (10.8 vs 6.6 mg/dL), IL-6 (60.3 vs 47.7 ng/L) and leukocyte count (7290 vs 6130 x109/L). Ferritin was higher in anemic patients at T0 and T1 (1220 vs 926 mcg/L and 852 vs 896 mcg/L, p ns), decreasing more at T2 (655 vs 763 mcg/L, p ns). Median hepcidin levels, which were available for a limited subset of non- ICU patients, were elevated during the whole period: 233 ng/mL at T0, 95 ng/mL at T1 and 60 ng/mL at T2. Summary/Conclusion: In patients with SARS-CoV-2 infection, two main factors influence erythropoiesis and iron homeostasis: systemic inflammation and profound hypoxia. Markedly high ferritin and hepcidin levels reflect a strong inflammatory response. However, COVID-19 patients tend to have disproportionately high Hb levels in the contest of the inflammatory milieu. The absolute reduction in Hb levels is more prominent in patients who displayed normal Hb on admission. Conversely, anemic and profoundly hypoxic subjects show constant mean Hb levels over time. Thus, we can hypothesize that the erythropoietic drive provided by hypoxia could counterbalance the effect of inflammation on hepcidin regulation, preventing Hb levels from falling dramatically during hospitalization.