New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID-19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

BACKGROUND Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease process is still lacking. METHODS Autopsies were performed at the Mount Sinai Hospital on 67 COVID-19 positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTS Laboratory results of our COVID-19 cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8 and TNFα. Autopsies revealed large pulmonary emboli in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis and a secondary hemophagocytic lymphohistiocytosis-like syndrome in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 receptor in our samples. CONCLUSIONS We report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome, with hemophagocytosis and a hemophagocytic lymphohistiocytosis-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.

Infection with the new pandemic pathogen Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) can cause a wide range of disease varying from mild cold-like symptoms to complicated pneumonia, severe inflammatory response, and death. 1 Although available data has been limited, recent case reports of concurrent infections with influenza virus, 2 human metapneumovirus (hMPV) 3 and seasonal coronaviruses such as CoV-HKU-1 4 in adults and children with SARS-CoV-2 infection have suggested that coinfection may influence morbidity and mortality. A recent study from Kim et al, 5 found that co-infections were frequent in their patient population in Northern California; more than 20% of 116 SARS-CoV-2 positive specimens also contained one or more additional respiratory pathogens, most often rhinovirus/enterovirus, respiratory syncytial virus, and non-SARS Coronaviridae.Conversely, 7.5% of their specimens positive for a non-SARS-CoV-2 respiratory pathogen were also positive for SARS-CoV-2. 5 In addition, a study from Wuhan examining 8274 patients with 2745 confirmed SARS-CoV-2 cases, revealed that 5.8% of SARS-CoV-2 infected and 18.4% of non-SARS-CoV-2-infected patients had co-infections. 6 To determine whether co-infections with other respiratory pathogens represent a significant subset of SARS-CoV-2 infections in our patient population, we reviewed results from our laboratory, which performs diagnostic testing for 8 inpatient and associated outpatient facilities in the greater New York City metropolitan area. tested 16,408 patients for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction amplification (RT-PCR, cobas® 6800 system, RocheDiagnostics); of those, 2,049 were also tested with the multiplex FilmArray® Respiratory Panel (RPPCR2, BioMerieux) or Cepheid Xpert® Xpress Flu/RSV (Flu/RSV). Our findings are notable for high rates of SARS-CoV-2 positivity (54.8 %) during that time period, and very low rates of co-infection with other non-SARS-CoV-2 pathogens. Specific data for the detection of other respiratory pathogens in our SARS-CoV-2 positive patients is presented in Table I, and compared to findings for patients in whom SARS-CoV-2 was not detected.This article is protected by copyright. All rights reserved.otherwise modified disease course. However, our results are in keeping with a recent paper from Spain showing that hospitalized SARS-CoV-2 patients with pneumonia were infrequently co-infected with other respiratory viruses. 7

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. Methods In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. Findings Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. Interpretation Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. Funding None.