COVID-19 disease, caused by SARS-CoV-2 infection, has resulted in more than 15.5 million infections and 634,000 deaths worldwide. A recent study of hospitals in New York City, at the initial epicenter of the COVID-19 pandemic in the United States, reported that, during March 2020, 21% of patients hospitalized with confirmed COVID-19 died 1 . These findings are aligned with outcomes observed in the Mount Sinai Health System 2,3 . There are currently no curative or preventive therapies for COVID-19, highlighting the need to enhance current understanding of SARS-CoV-2 pathogenesis for the rational development of therapeutics.Recent studies have suggested that, in addition to direct viral damage, uncontrolled inflammation contributes to disease severity in 5 ). Consistent with this hypothesis, high levels of inflammatory markers, including C-reactive protein (CRP), ferritin and D-dimer, high neutrophil-to-lymphocyte ratio [6][7][8][9] and increased levels of inflammatory cytokines and chemokines 6,8-11 have been observed in patients with severe diseases. Pathogenic inflammation, also referred to as cytokine storm, shares similarities with what was previously seen in patients infected with other severe coronaviruses, including SARS-CoV and Middle East respiratory syndrome coronavirus 12 , and bears similarities to cytokine release syndrome (CRS) observed in patients with cancer treated with chimeric antigen receptor-modified (CAR) T cells 13 . Tocilizumab, an IL-6 receptor inhibitor, is a US Food and Drug Administration (FDA)-approved treatment for CRS in patients receiving CAR T cells 14 . Several single-center studies have used IL-6 inhibitors to treat patients with COVID-19 with some clinical benefits 15 and reported failures 14 . Beyond IL-6, several cytokines have been shown to be elevated in CRS and to contribute to tissue damage. TNF-α is important in nearly all acute inflammatory reactions, acting as an amplifier of inflammation. TNF-α blockade has been used to treat more than ten different autoimmune inflammatory diseases, suggesting that this might be a potential therapeutic approach to reduce organ damage in patients with ). IL-1 is also a highly active pro-inflammatory cytokine, and monotherapy blocking

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City. We also show that titers are relatively stable for at least a period approximating 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments 1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses 2,3. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed 1,2. This retrospective, propensity score-matched case-control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score-matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75-0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13-0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed.

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.