Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods.

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods. Design, Setting, and Participants: This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022. Exposures: mRNA COVID-19 vaccination. Main Outcomes and Measures: The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods. Results: During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17). Conclusions and Relevance: In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir.

Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-191,2. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities3-9, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both, and their sequences revealed a multitude of 3CL protease mutations. In the experiment done with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. Yet, several common mutational pathways to nirmatrelvir resistance were preferred, with a majority of the viruses descending from T21I, P252L, or T304I as precursor mutations. Construction and analysis of 13 recombinant SARS-CoV-2 clones showed that these mutations only mediated low-level resistance, whereas greater resistance required accumulation of additional mutations. E166V mutation conferred the strongest resistance (~100-fold), but this mutation resulted in a loss of viral replicative fitness that was restored by compensatory changes such as L50F and T21I. Our findings indicate that SARS-CoV-2 resistance to nirmatrelvir does readily arise via multiple pathways in vitro, and the specific mutations observed herein form a strong foundation from which to study the mechanism of resistance in detail and to inform the design of next generation protease inhibitors.

Reduction in Risk of Death Among Patients Admitted With COVID-19 Between the First and Second Epidemic Waves in New York City.

Background: Many regions have experienced successive epidemic waves of coronavirus disease 2019 (COVID-19) since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. Methods: We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-August 2020) and second (August 2020-March 2021) epidemic waves at an academic medical center in New York City. Results: Hospitalized patients (n = 4631) had lower overall and 30-day in-hospital mortality, defined as death or discharge to hospice, during the second wave (14% and 11%) than the first (22% and 21%). The wave 2 in-hospital mortality decrease persisted after adjusting for several potential confounders. Adjusting for the volume of COVID-19 admissions, a measure of health system strain, accounted for the mortality difference between waves. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave: SARS-CoV-2 cycle threshold, do-not-intubate status, oxygen requirement, and intensive care unit admission. Conclusions: This work suggests that the increased in-hospital mortality rates observed during the first epidemic wave were partly due to strain on hospital resources. Preparations for future epidemics should prioritize evidence-based patient risks, treatment paradigms, and approaches to augment hospital capacity.

Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City

Background Many regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. Methods We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-August 2020) and second (August 2020-March 2021) epidemic waves at an academic medical center in New York City. Results Hospitalized patients (N = 4631) had lower overall and 30-day in-hospital mortality, defined as death or discharge to hospice, during the second wave (14% and 11%) than the first (22% and 21%). The wave 2 in-hospital mortality decrease persisted after adjusting for several potential confounders. Adjusting for the volume of COVID-19 admissions, a measure of health system strain, accounted for the mortality difference between waves. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave;SARS-CoV-2 cycle threshold, Do-Not-Intubate status, oxygen requirement, and intensive care unit admission. Conclusions This work suggests that increased in-hospital mortality rates observed during the first epidemic wave were partly due to strain on hospital resources. Preparations for future epidemics should prioritize evidence-based patient risks, treatment paradigms, and approaches to augment hospital capacity.

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a ≥2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

Development and performance of a point-of-care rapid antigen test for detection of SARS-COV-2 variants.

Background: SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA). Methods: Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2 nucleocapsid protein (NP) were isolated, evaluated, and chosen for the development of a LFA termed CoV-SCAN (BioMedomics, Inc.). Clinical point-of-care studies in symptomatic and asymptomatic individuals were conducted to evaluate positive predictive agreement (PPA) and negative predictive agreement (NPA) with RT-PCR as comparator. Results: In laboratory testing, CoV-SCAN detected 14 recombinant N-proteins of SARS-CoV-2 variants with sensitivity in the range of 0.2-3.2 ng/mL, and 10 authentic SARS-CoV-2 variants with sensitivity in the range of 1.6-12.5 TCID50/swab. No cross reactivity was observed with other human coronaviruses or other respiratory pathogens. In clinical point-of-care testing on 148 individuals over age 2 with symptoms of ≤5 days, PPA was 87.2% (CI 95: 78.3-94.8%) and NPA was 100% (CI 95: 94.2-100%). In another 884 asymptomatic individuals, PPA was 85.7% (CI 95: 42.1-99.6%) and 99.7% (99.0-99.9%). Overall, CoV-SCAN detected over 97.2% of specimens with CT values <30 and 93.8% of nasal swab specimens with the Omicron variant, even within the first 2 days after symptom onset. Conclusions: The unique construction of CoV-SCAN using two pairs of monoclonal antibodies has resulted in a test with high performance that remains durable across multiple variants in both laboratory and clinical evaluations. CoV-SCAN should identify almost all individuals harboring infectious SARS-CoV-2. Summary: Unique construction of a point-of-care rapid antigen test using two pairs of monoclonal antibodies has led to good performance that remained durable across multiple variants in laboratory and clinical evaluations. Test should identify almost all individuals harboring infectious SARS-CoV-2.

Clinico-histopathologic and single-nuclei RNA-sequencing insights into cardiac injury and microthrombi in critical COVID-19.

Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes - myocarditis and cardiac necrosis - have proved uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at CUIMC in New York City. Of 6 acute cardiac histopathologic features, presence of microthrombi was the most commonly detected among our cohort. We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and C-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single-nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of prothrombotic/antifibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling among cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19, nonfailing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.

Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (n = 53) and controls (n = 59) and based on saliva SARS-CoV-2 viral load as measured using reverse transcription PCR (RT-PCR). The saliva microbiome did not differ markedly between COVID-19 patients and controls. However, we identified significant differential abundance of numerous taxa based on saliva SARS-CoV-2 viral load, including multiple species within Streptococcus and Prevotella. IMPORTANCE Alterations to the saliva microbiome based on SARS-CoV-2 viral load indicate potential biologically relevant bacterial-viral relationships which may affect clinical outcomes in COVID-19 disease.

SARS-CoV-2 RNA Shedding in Semen and Oligozoospermia of Patient with Severe Coronavirus Disease 11 Weeks after Infection.

We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.

Emergence and expansion of SARS-CoV-2 B.1.526 after identification in New York.

SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature spike mutations of concern are E484K, which has a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here we report the emergence of the variant lineage B.1.526 (also known as the Iota variant5), which contains E484K, and its rise to dominance in New York City in early 2021. This variant is partially or completely resistant to two therapeutic monoclonal antibodies that are in clinical use and is less susceptible to neutralization by plasma from individuals who had recovered from SARS-CoV-2 infection or serum from vaccinated individuals, posing a modest antigenic challenge. The presence of the B.1.526 lineage has now been reported in all 50 states in the United States and in many other countries. B.1.526 rapidly replaced earlier lineages in New York, with an estimated transmission advantage of 35%. These transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, are likely to have contributed to the sharp rise and rapid spread of B.1.526. Although SARS-CoV-2 B.1.526 initially outpaced B.1.1.7 in the region, its growth subsequently slowed concurrently with the rise of B.1.1.7 and ensuing variants.

Prolonged severe acute respiratory syndrome coronavirus 2 persistence, attenuated immunologic response, and viral evolution in a solid organ transplant patient

Abstract Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence at 138 days with low polymerase chain reaction cycle threshold values and evidence of continuing viral sequence evolution indicative of ongoing virus replication. These findings have important implications for infection prevention and control recommendations in immunosuppressed patients. Immune response, including neutralizing antibody titers, T cell activity, and cytokine levels, peaked around days 44-72 after diagnosis. Anti-S trimer antibodies were low at all time points, and T cell response was attenuated by day 119. As immune response waned and viral load increased, increased genetic diversity emerged, suggesting a mechanism for the development of viral variants.

Supervised Machine Learning Approach to Identify Early Predictors of Poor Outcome in Patients with COVID-19 Presenting to a Large Quaternary Care Hospital in New York City.

BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care-associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. METHODS: We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs. RESULTS: A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs. CONCLUSIONS: HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.

Outcomes of COVID-19 in solid organ transplant recipients: A matched cohort study.

Whether solid organ transplant (SOT) recipients are at increased risk of poor outcomes due to COVID-19 in comparison to the general population remains uncertain. In this study, we compared outcomes of SOT recipients and non-SOT patients hospitalized with COVID-19 in a propensity score matched analysis based on age, race, ethnicity, BMI, diabetes, and hypertension. After propensity matching, 117 SOT recipients and 350 non-SOT patients were evaluated. The median age of SOT recipients was 61 years, with a median time from transplant of 5.68 years. The most common transplanted organs were kidney (48%), followed by lung (21%), heart (19%), and liver (10%). Overall, SOT recipients were more likely to receive COVID-19 specific therapies and to require ICU admission. However, mortality (23.08% in SOT recipients vs. 23.14% in controls, P = .21) and highest level of supplemental oxygen (P = .32) required during hospitalization did not significantly differ between groups. In this propensity matched cohort study, SOT recipients hospitalized with COVID-19 had similar overall outcomes as non-SOT recipients, suggesting that chronic immunosuppression may not be an independent risk factor for poor outcomes in COVID-19.

COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital.

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.

What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak.

BACKGROUND: Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease. METHODS: In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test. RESULTS: We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168). CONCLUSIONS: There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab.

Pretest Symptom Duration and Cycle Threshold Values for Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-Transcription Polymerase Chain Reaction Predict Coronavirus Disease 2019 Mortality.

BACKGROUND: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted an observational study between March 10 and May 30, 2020 at a large quaternary academic medical center in New York City. Patient characteristics, laboratory values, and clinical outcomes were abstracted from the electronic medical records. Of all patients tested for SARS-CoV-2 during this time (N = 16 384), there were 5467 patients with positive tests, 4254 of which had available cycle threshold (Ct) values and were included in further analysis. Univariable and multivariable logistic regression models were used to test associations between Ct values, duration of symptoms before testing, patient characteristics, and mortality. The primary outcome is defined as death or discharge to hospice. RESULTS: Lower Ct values at diagnosis (ie, higher viral load) were associated with significantly higher mortality among both in- and outpatients. It is interesting to note that patients with a shorter time since the onset of symptoms to testing had a worse prognosis, with those presenting less than 3 days from symptom onset having 2-fold increased odds of death. After adjusting for time since symptom onset and other clinical covariates, Ct values remained a strong predictor of mortality. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction Ct value and duration of symptoms are strongly associated with mortality. These 2 factors add useful information for clinicians to risk stratify patients presenting with COVID-19.

Limited Utility of Procalcitonin in Identifying Community-Associated Bacterial Infections in Patients Presenting with Coronavirus Disease 2019.

The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2,443 patients of whom 148 had bacterial coinfections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/ml; P = 0.0091) and with bacteremia (34.25 ± 85.01 ng/ml; P = 0.0125) than without infection (2.00 ± 15.26 ng/ml). Procalcitonin (cutoff, 0.25 or 0.50 ng/ml) did not reliably identify bacterial coinfections but may be useful in excluding bacterial infection.

Trophoblast damage with acute and chronic intervillositis: disruption of the placental barrier by severe acute respiratory syndrome coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was demonstrated in the placenta; however, the data on the prevalence of placental infection and associated histopathology are limited. To identify the frequency and features of SARS-CoV-2 involvement, we performed a clinicopathologic analysis of 75 placental cases from women infected at the time of delivery and 75 uninfected controls. Placental samples were studied with anti-SARS-CoV-2 immunohistochemistry and/or in situ hybridization. Positive results were confirmed by electron microscopy and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). During delivery, only one woman had symptoms of coronavirus disease 2019, six women reported previous symptoms, and 68 women were asymptomatic. All neonates tested negative for SARS-CoV-2 as per nasopharyngeal swab PCR results. Obstetric histories were unremarkable in 29 of 75 SARS-CoV-2-positive and 8 of 75 SARS-CoV-2-negative women. Placental examination was normal in 12 of 75 infected and 3 of 75 uninfected subjects, respectively. In the remaining cases, placental pathology correlated with obstetric comorbidities without significant differences between SARS-CoV-2-positive and SARS-CoV-2-negative women. SARS-CoV-2 was identified in one placenta of an infected, but asymptomatic, parturient. Viral staining was predominantly localized to the syncytiotrophoblast (STB) which demonstrated marked damage accompanied by perivillous fibrin deposition and mixed intervillositis. A significant decrease of viral titers was detected in the attached umbilical cord compared with the villous parenchyma as per qRT-PCR. SARS-CoV-2 is seldom identified in placentas of infected women. Placental involvement by the virus is characterized by STB damage disrupting the placental barrier and can be seen in asymptomatic mothers without evidence of vertical transmission.