Characterization of Patients Who Return to Hospital Following Discharge from Hospitalization For COVID-19 (preprint)

Background: Data on patients with coronavirus disease 2019 (COVID-19) who return to hospital after discharge are scarce. Characterization of these patients may inform post-hospitalization care. Methods and Findings: Retrospective cohort study of patients with confirmed SARS-CoV-2 discharged alive from five hospitals in New York City with index hospitalization between February 27th-April 12th, 2020, with follow-up of [≥]14 days. Significance was defined as P<0.05 after multiplying P by 125 study-wide comparisons. Of 2,864 discharged patients, 103 (3.6%) returned for emergency care after a median of 4.5 days, with 56 requiring inpatient readmission. The most common reason for return was respiratory distress (50%). Compared to patients who did not return, among those who returned there was a higher proportion of COPD (6.8% vs 2.9%) and hypertension (36% vs 22.1%). Patients who returned also had a shorter median length of stay (LOS) during index hospitalization (4.5 [2.9,9.1] vs. 6.7 [3.5, 11.5] days; Padjusted=0.006), and were less likely to have required intensive care on index hospitalization (5.8% vs 19%; Padjusted=0.001). A trend towards association between absence of in-hospital anticoagulation on index admission and return to hospital was also observed (20.9% vs 30.9%, Padjusted=0.064). On readmission, rates of intensive care and death were 5.8% and 3.6%, respectively. Conclusions: Return to hospital after admission for COVID-19 was infrequent within 14 days of discharge. The most common cause for return was respiratory distress. Patients who returned had higher proportion of COPD and hypertension with shorter LOS on index hospitalization, and a trend towards lower rates of in-hospital treatment-dose anticoagulation. Future studies should focus on whether these comorbid conditions, longer LOS and anticoagulation are associated with reduced readmissions.

Identification of Immune complement function as a determinant of adverse SARS-CoV-2 infection outcome (preprint)

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutics and public health intervention strategies. Viral-host interactions can guide discovery of regulators of disease outcomes, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of the coronavirus proteome. To determine if conditions associated with dysregulation of the complement or coagulation systems impact adverse clinical outcomes, we performed a retrospective observational study of 11,116 patients who presented with suspected SARS-CoV-2 infection. We found that history of macular degeneration (a proxy for complement activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis, and hemorrhage) are risk factors for morbidity and mortality in SARS-CoV-2 infected patients - effects that could not be explained by age, sex, or history of smoking. Further, transcriptional profiling of nasopharyngeal (NP) swabs from 650 control and SARS-CoV-2 infected patients demonstrated that in addition to innate Type-I interferon and IL-6 dependent inflammatory immune responses, infection results in robust engagement and activation of the complement and coagulation pathways. Finally, we conducted a candidate driven genetic association study of severe SARS-CoV-2 disease. Among the findings, our scan identified putative complement and coagulation associated loci including missense, eQTL and sQTL variants of critical regulators of the complement and coagulation cascades. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multi-modal analytical approach, combining molecular information from virus protein structure-function analysis with clinical informatics, transcriptomics, and genomics to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with infection.