Early COVID-19 Infection Research Articles

Impaired Immune Reconstitution and Worse Survival Outcomes Among Allogeneic Stem Cell Transplant Patients with Early COVID-19 Infection

Impaired Immune Reconstitution and Worse Survival Outcomes Among Allogeneic Stem Cell Transplant Patients with Early COVID-19 Infection

IODINE AS A POTENTIAL FRONT-LINE DEFENSE AGAINST COVID-19: A LITERATURE REVIEW

The novel coronavirus disease, first identified in 2019 known as COVID-19, is caused by a new strain of severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), named SARS-CoV-2. Recent studies showed that the virus may be airborne and spreads through small respiratory droplets of saliva in aerosols, indirect or direct physical contact with the affected individual, in a similar way to the cold and influenza. Emerging studies also demonstrate the importance of the throat along with salivary glands as sites of viral replication and transmission in early COVID-19 infection. The most common route of entry of SARS-CoV-2 is the upper respiratory tract (nasopharynx) that slowly reaches the lower respiratory tract to infect the epithelial cells within the lungs which can cause lung damage and severe respiratory symptoms, if not treated immediately. Averting colonization of the virus in the nasopharynx could be one of the best options to reduce the incidence of severe infection. It has been well-documented that iodine is one of the most effective of all antimicrobials available. Hospitals and medical facilities worldwide use povidone-iodine (PVP-I) as a standard of care in infection control. Several research studies during the ongoing COVID-19 pandemic showed the in vitro and in vivo efficacy of iodine-containing solutions such as PVP-I (Betadine), Iodine-V (Essential Iodine Drops) etc. and other iodine complexes to effectively kill the SARS-CoV-2 virus within few seconds to hours. Few commercially available iodine-containing gargling, mouthwash, and nasal spray solutions have been recommended to use in humans against SARS-CoV-2 infection by experts to prevent viral spread, especially among health workers. The present article aims to summarize these studies and highlights the rationale, safety and recommendations of use of iodine as an effective method to decrease the viral load during the early COVID-19 infection.

Assessment of C-reactive protein levels as an indicator for lung infiltrates in patients with COVID-19 pneumonia.

Lung infiltrates are frequently observed in patients with COVID-19 infection and require specialized management. Identifying reliable laboratory parameters to reduce the need for chest CT scans in non-desaturation patients is of great interest. This study aimed to investigate the potential of C-reactive protein (CRP) as an indicator to identify the presence of lung infiltrates in early COVID-19 infection. The study was conducted at Al-Azhar University hospitals from May 2021 to March 2022 and included 210 patients with COVID-19 infection confirmed by positive PCR, all of whom were previously healthy, non-smokers, and non-hypoxemic. CRP levels were assessed and correlated with lung infiltrates observed in CT chest examinations. The mean value of CRP was 40.3±14.3 mg/L in males and 36.6±15.2 mg/L among females. One hundred sixty-two patients had pneumonic infiltrates, while 48 had no infiltrates. The mean value of CRP was 45.02±10.2 mg/L in patients with radiological infiltrates and 18.8±7.8 mg/L in patients without radiological infiltrates. Based on our findings, a CRP value greater than 29.8 mg/L was suggested as a cut-off value to indicate the presence of lung infiltrates. CRP is a simple laboratory marker that, at certain limits, may point to the presence of pneumonic infiltrates in early non-hypoxemic patients with COVID-19 infection.

Photodynamic therapy (pdt) in early stages of acute adult covid-19 patients: effects on viral load measured by qpcr

Background: The Covid-19 pandemic has negatively impacted Global Health and the world’s economy dramatically since early 2020. Although the development of vaccines has made fast progress, there are currently only a few effective medications and treatment options available for infected patients available. Objectives: The objective of this study was to evaluate the efficacy and safety of Photodynamic Therapy (PDT) with Riboflavin and a specially designed light treatment kit with blue and UVA light as a treatment tool for reducing viral load and clinical symptoms in patients with early stage Covid-19 infection. Methods: This interventional, non-randomized study involved 140 adult subjects. Participants were allocated to receive either PDT plus daily testing for 5 days or to receive conventional care plus testing. The viral load in the oral and nasal cavity and clinical symptoms were measured at the start of the study and after 24,48,72,96,120 and 168 hours. Results: The mean CT value in the treatment group was 29.63 at day 1 and 36.3 at day 5, for a difference of 6.68 threshold cycles and a confidence interval of [5.2;8.72]. Based on Welch’s t-test for two samples, this difference was significant (p<0.01). The same test showed no difference in the means of the control group. Further analysis showed a significant difference between the treatment and control group in the clinical symptoms after 5 days as well, when controlled for the differences at the beginning. Conclusion: PDT decreases viral load and improves clinical symptoms in patients in early stages of Covid-19 significantly. It could be a promising tool for treatment of acutely infected patients in early stages to prevent progression of disease.

Oral anti-viral therapy for early COVID-19 infection in patients with haematological malignancies: A multicentre prospective cohort.

High rates of lung failure have been reported in haematological patients after SARS-CoV2 infection. An early administration of monoclonal antibodies or anti-virals may improve the prognosis. Oral anti-virals may have a wider use independently of the genetic variations of the virus. Prospective data on anti-virals in haematological malignancies (HMs) are still lacking. Outpatients diagnosed with HM and early COVID-19 infection were prospectively treated with the oral anti-virals nirmatrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse events was analysed. Long-term outcome at third month was evaluated. Eighty-two outpatients were evaluable for the study objectives. All patients had been treated for their HM within 12 months. COVID-19-related lung failure was 23.1%. Active HM (aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted independent predictors of severe infection. The vaccination with three to four doses (aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protective. COVID-19-related deaths at 28 days were 6.1%. All-cause mortality at 90-day follow-up was 13.4% (n. 11) and included opportunistic infections and cardiovascular events. In conclusion, this approach reduced the incidence of lung failure and specific mortality compared to previous cohorts, but patients remain at high risk of further complications.

A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection.

Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. At the University of Utah, Salt Lake City, Utah, we conducted a phase 2 prospective parallel group randomized placebo-controlled trial (NCT04342169) to determine whether hydroxychloroquine given early in disease reduces the duration of SARS-CoV-2 shedding. We enrolled nonhospitalized adults (≥18 years of age) with a recent positive diagnostic test for SARS-CoV-2 (within 72 h of enrollment) and adult household contacts. Participants received either 400 mg hydroxychloroquine by mouth twice daily on day 1 followed by 200 mg by mouth twice daily on days 2 to 5 or oral placebo with the same schedule. We performed SARS-CoV-2 nucleic acid amplification testing (NAAT) on oropharyngeal swabs on days 1 to 14 and 28 and monitored clinical symptomatology, rates of hospitalization, and viral acquisition by adult household contacts. We identified no overall differences in the duration of oropharyngeal carriage of SARS-CoV-2 (hazard ratio of viral shedding time comparing hydroxychloroquine to placebo, 1.21; 95% confidence interval [CI], 0.91, 1.62). Overall, 28-day hospitalization incidence was similar between treatments (4.6% hydroxychloroquine versus 2.7% placebo). No differences were seen in symptom duration, severity, or viral acquisition in household contacts between treatment groups. The study did not reach the prespecified enrollment target, which was likely influenced by a steep decline in COVID-19 incidence corresponding to the initial vaccine rollout in the spring of 2021. Oropharyngeal swabs were self-collected, which may introduce variability in these results. Placebo treatments were not identical to hydroxychloroquine treatments (capsules versus tablets) which may have led to inadvertent participant unblinding. In this group of community adults early in the COVID-19 pandemic, hydroxychloroquine did not significantly alter the natural history of early COVID-19 disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT04342169). IMPORTANCE Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. Hydroxychloroquine received attention as a possible early treatment; however, quality prospective studies were lacking. We conducted a clinical trial to test the ability of hydroxychloroquine to prevent clinical worsening of COVID-19.

Masking in early child care and COVID-19 infection

Masking, a common SARS-CoV-2 risk mitigation strategy, is controversial for children in educational settings such as childcare. A prospective survey of early childcare workers demonstrated that child masking was associated with a significant reduction in COVID-19 program closure, highlighting potential benefits of child masking in keeping childcare open, parents employed, and children learning.

Use of convalescent plasma in pregnant women with early stage COVID-19 infection in a tertiary care hospital in Dubai, February to March 2021: a case series study

BackgroundThe use of COVID-19 convalescent plasma (CCP) for the treatment of SARS-CoV-2 infection in pregnancy is intriguing in view of its safety profile in pregnancy and historical precedence of the use of plasma for other viral illnesses. This study aimed to evaluate the use of CCP in pregnant women with early COVID-19 infection.MethodsThis is a retrospective case series study. We have included seven pregnant women admitted with early COVID-19 infection to a tertiary care hospital, Latifa Maternity Hospital in Dubai, United Arab Emirates between 12 February and 04 March 2021 and who consented to receive COVID-19 convalescent plasma as part of their treatment plan. Main outcomes measured were clinical and radiological features, laboratory tests, WHO clinical progression scale pre and post treatment, and maternal, fetal outcomes. COVID-19 clinical severity was classified according to the NIH guidelines for criteria of SARS-CoV-2. For the radiological features, a modified chest X-ray scoring system was used where each lung was divided into 6 zones (3 on each side upper, middle, and lower). Opacities were classified into reticular, ground glass, patchy and dense consolidations patterns.ResultsSeven pregnant women with early COVID-19 were enrolled in this study, their mean age was 28 years (SD 3.6). Four had comorbidities: 2 with diabetes, 1 with asthma, and 1 was obese. Five patients were admitted with a WHO clinical progression score of 4 (hospitalized; with no oxygen therapy) and 2 with a score of 5 (hospitalized; oxygen by mask/nasal prongs). Upon follow up on day 10, 6 patients had a WHO score of 1 or 2 (asymptomatic/mild symptoms) indicating clinical recovery. Adverse reactions were reported in 2 patients, one reported a mild skin rash, and another developed transfusion related circulatory overload. All patients were discharged alive.ConclusionCCP seems to be a promising modality of treating COVID-19 infected pregnant women. However, further studies are needed to ascertain the efficacy of CCP in preventing progressive disease in the management of COVID-19 infection in pregnant women.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study

BackgroundThe SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.MethodsCRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country.FindingsFrom June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1–3 in 445 (44%) participants, 4–5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05–2·92) unadjusted and 1·67 (1·34–2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60–2·01) when unadjusted and 1·63 (1·41–1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6–77·1%) for mortality (threshold 0·47) and 67·4% (64·4–70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5–95% percentile interval 0·730–1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04).InterpretationThe urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1–4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs.FundingGerman Federal Ministry of Health.

Oral Drugs Against COVID-19.

Five-day oral therapies against early COVID-19 infection have recently been conditionally approved in Europe. In the drug combination nirmatrelvir + ritonavir (nirmatrelvir/r), the active agent, nirmatrelvir, is made bioavailable in clinically adequate amounts by the additional administration of a potent inhibitor of its first-pass metabolism by way of cytochrome P450 [CYP] 3A in the gut and liver. In view of the central role of CYP3A in the clearance of many different kinds of drugs, and the fact that many patients with COVID-19 are taking multiple drugs to treat other conditions, it is important to assess the potential for drug interactions when nirmatrelvir/r is given, and to minimize the risks associated with such interactions. We defined the interaction profile of ritonavir on the basis of information derived from two databases (Medline, GoogleScholar), three standard electronic texts on drug interactions, and manufacturer-supplied drug information. We compiled a list of drugs and their potentially relevant interactions, developed a risk min - imization algorithm, and applied it to the substances in question. We also compiled a list of commonly prescribed drugs for which there is no risk of interaction with nirmatrelvir/r. Out of 190 drugs and drug combinations, 57 do not need any special measures when given in combination with brief, low-dose ritonavir treatment, while 15 require dose modification or a therapeutic alternative, 8 can be temporarily discontinued, 9 contraindicate ritonavir use, and 102 should preferably be combined with a different treatment. We have proposed measures that are simple to carry out for the main types of drug that can interact with ritonavir. These measures can be implemented under quarantine conditions before starting a 5-day treatment with nirmatrelvir/r.

Monoclonal antibody infusion for COVID-19 infection: results from a tertiary referral center

Monoclonal antibody infusion with bamlanivimab or casirivimab/imdevimab for early COVID-19 infection has been shown in small studies to be effective at preventing hospitalization in high risk patients. We reviewed and present our experience at BJC Healthcare with monoclonal antibody infusion for this indication.

COVID-19 in Recent Lung Transplant Recipients: Clinical Outcomes and Management Strategies

BackgroundCOVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation.MethodsWe describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes.ResultsThree of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma.ConclusionsCOVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.

Predictive Performance and Clinical Application of COV50,&amp;nbsp;A Urinary Proteomic Biomarker in Early COVID-19 Infection:&amp;nbsp;A Cohort Study

Predictive Performance and Clinical Application of COV50,&amp;nbsp;A Urinary Proteomic Biomarker in Early COVID-19 Infection:&amp;nbsp;A Cohort Study

Collective Reactions to Epidemic Threat: Attachment and Cultural Orientations Predict Early COVID-19 Infection and Mortality Rates and Trajectories

Hypotheses on culture-level attachment and individualism/collectivism relationships with COVID-19 infection and death rates during a period at the beginning of the epidemic were tested in data from 53 countries and 50 U.S. states. Results from multilevel growth curve analyses showed group-average anxious attachment predicted a lower initial number of cases and deaths cross-culturally and in the United States, while avoidant attachment predicted a higher initial number of COVID-19 infections in the United States and a higher initial number of deaths in both studies. Yet, during this period, culture-level anxious attachment was associated with a higher growth rate of infections and deaths, while a lower growth rate of infections and deaths was observed in countries and U.S. states with higher individualism and avoidance. The research provides new insights into attachment and culture relationships and points to different mechanisms that may explain initial and growth rate trajectories at the beginning of the epidemic.

926. COVID-19 Infections After SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients

BackgroundSolid organ transplant recipients (SOTR) have lower humoral responses following SARS-CoV-2 vaccination. Whether this equates to reduced vaccine effectiveness in SOTR or impacts disease severity is not yet known. We used the IDSA Emerging Infections Network (EIN) to identify SARS-CoV-2 cases in vaccinated SOTR. We describe their clinical characteristics and outcomes.MethodsOn 4/7/21, we requested case reports via the EIN listserv of COVID-19 infection following SARS-CoV-2 vaccination in immunocompromised individuals. Case reports were collected until June 7th. Online data collection included patient demographics, dates of SARS-CoV-2 vaccine administration and clinical data related to COVID-19 infection. We performed a descriptive analysis of these patient factors and compared differences between early onset (< / = 21 days after completing vaccine series) and late onset infection ( > 21 days after completing vaccine series).ResultsAs of 6/7/21, 34 cases of COVID-19 infection after vaccination in SOTR were submitted. Most cases (79%) occurred in individuals who were fully vaccinated. Only 3 cases (8.5%) occurred in SOTR within their first year after transplantation. Clinical characteristics are listed in Table 1. The vaccine administration date was known for 26 SOTR among whom symptoms occurred a median of 26.5 days (IQR 21.75 days, range 5-79 days) after completing the COVID-19 vaccine series. Twenty-three SOTR (68%) required hospitalization of which 12 had critical illness. Outcome data was available for 29 individuals of whom 20 (69%) demonstrated improvement. When comparing SOTR with early versus late onset COVID-19 infection in relation to vaccination timing, there were no differences in disease severity (80% vs 75% with severe or critical disease, p=NS) or outcome (30% vs 31% died or deteriorating, p=NS).Table 1: Characteristics of Solid Organ Transplant Recipients with COVID-19 Infection Following SARS-CoV-2 Vaccination ConclusionSARS-CoV-2 infections after vaccination are occurring in SOTR, including cases of critical illness, suggesting reduced vaccine effectiveness within this vulnerable population. We did not appreciate any correlation between time from vaccination and COVID-19 disease severity or outcome. Further studies evaluating the true incidence of and risk factors for breakthrough infections among vaccinated SOTR are needed.Disclosures Matthew Kuehnert, M.D., American Association of Tissue Banks (Board Member)ICCBBA (Board Member)Musculoskeletal Transplant Foundation (Employee) John W. Baddley, M.D., Eli Lilly (Consultant)Pfizer (Consultant)R-Pharm (Consultant)Viela Bio (Consultant)

CLINICAL OUTCOMES IN LUNG TRANSPLANT RECIPIENTS WITH SARS-COV-2

TOPIC: Transplantation TYPE: Fellow Case Reports INTRODUCTION: SARS-CoV2, commonly known as COVID-19, has been noted to manifest severe illness in certain patient populations. The clinical manifestations of this coronavirus in solid organ transplant recipients is just beginning to be described, and is not well understood. SARS-CoV2 and associated illness have been described in multiple patient populations, so far limited data has been published on the course of illness in lung transplant recipients. Here we present a case series of 26 patients who were unfortunately infected with SARS-CoV2. CASE PRESENTATION: We conducted a single-center, retrospective review of 26 lung transplant recipients infected with SARS-CoV2. Data collection and patient consent were covered by OSU IRB protocol. DISCUSSION: 15 of these patients (55.5%) required admission for hypoxemia, and 4 required intubation and mechanical ventilation. 1 patient required extracorporeal membrane oxygenation (ECMO). 46% (12/26) patients received dexamethasone and remdesivir, 27% (7/26) received convalescent plasma, 1 received hydroxychloroquine, and 2 received azithromycin as part of their treatments. Prior to COVID-19 infection all patients but 1 were on a standard triple immune suppression regimen with calcineurin inhibitors, steroids, and cell cycle inhibitors. Calcineurin dosing was decreased in 2 patients with severe COVID-19 and cell cycle inhibitors were reduced by 50% or held for 2 weeks 50% patients. 1 patient succumbed to COVID-19 ARDS despite ECLS support and a second 3 months after initial diagnosis due to a massive CVA. Mortality 3 months after initial diagnosis was 7.6% which is lower than other reported series. The average change in FEV1 was a loss of 0.52 liters. An average loss of 0.69 liters of FVC was noted in survivors. CONCLUSIONS: To our knowledge this is one of the largest currently reported case series of lung transplant recipients with SARS-CoV2. Overall, mortality was higher in this group than in the general population but at 7.6% 3 months after diagnosis is lowest of the single center reports published. As expected, a decrease in lung function was noted in survivors. Three was no general difference in lung function in patients who received certain treatments over others. REFERENCE #1: Tsuang WM, Budev MM. COVID-19 and lung transplant patients. Cleve Clin J Med. 2020. REFERENCE #2: Aigner C, Dittmer U, Kamler M, Collaud S, Taube C. COVID-19 in a lung transplant recipient. J Heart Lung Transplant. 2020;39(6):610-611. REFERENCE #3: Keller BC, Le A, Sobhanie M, et al. Early COVID-19 infection after lung transplantation. Am J Transplant. 2020;20(10):2923-2927. DISCLOSURES: No relevant relationships by Mena Botros, source=Web Response No relevant relationships by Molly Howsare, source=Web Response

Employment impacts of the COVID‐19 pandemic across metropolitan status and size

We use individual‐level data from the United States Current Population Survey to examine effects of the COVID‐19 pandemic on employment losses across metropolitan area status and population size. Job losses spiked in April 2020, and partially recovered in subsequent months. Non‐metropolitan and metropolitan areas of all sizes experienced significant employment losses, but the impacts were much larger in large metropolitan areas. The COVID‐19 infection rate was initially higher in large metropolitan areas and this is a significant factor explaining the higher early employment losses in large metropolitan areas. However, higher job losses for large metropolitan areas persisted through summer and fall 2020 even after COVID‐19 infection rates became higher in less populous areas. We find evidence of persistent effects of early COVID‐19 infection rates on later employment.

A Bayesian estimate of the early COVID-19 infection fatality ratio in Brazil based on a random seroprevalence survey

Background:A number of estimates of the infection fatality ratio (IFR) of SARS-CoV-2 in different countries have been published. In Brazil, the fragile political situation, together with socioeconomic and ethnic diversity, could result in substantially different IFR estimates.Methods:We infer the IFR in Brazil in 2020 by combining three datasets. We compute the prevalence via the population-based seroprevalence survey, EPICOVID19-BR. For the fatalities we obtain the absolute number using the public Painel Coronavírus dataset and the age-relative number using the public SIVEP-Gripe dataset. The time delay between the development of antibodies and subsequent fatality is estimated via the SIVEP-Gripe dataset. We obtain the IFR for each survey stage and 27 federal states. We include the effect of fading IgG antibody levels by marginalizing over the test detectability time window.Results:We infer a country-wide average IFR (maximum posterior and 95% CI) of 1.03% (0.88–1.22%) and age-specific IFRs of 0.032% (0.023–0.041%) [< 30 years], 0.22% (0.18–0.27%) [30–49 years], 1.2% (1.0–1.5%) [50–69 years], and 3.0% (2.4–3.9%) [≥ 70 years]. We find that the fatality ratio in the country increased significantly at the end of June 2020, likely due to the increased strain on the health system.Conclusions: Our IFR estimate is based on data and does not rely on extrapolating models. This estimate sets a baseline value with which future medications and treatment protocols may be confronted.

Mapping each pre-existing condition\u2019s association to short-term and long-term COVID-19 complications

Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage ~1.1 million clinical notes from 1803 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0–30 days, 31–60 days, and 61–90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (89/1803 patients, 4.9%) followed by cardiac arrhythmia (45/1803 patients, 2.5%). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia, and anemia. The onset of new complications after 30 days is rare and most commonly involves pleural effusion (31–60 days: 11 patients, 61–90 days: 9 patients). Lastly, comparing the rates of complications with a propensity-matched COVID-negative hospitalized population confirmed the importance of hypertension as a risk factor for early-onset complications. Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways.

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality.

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.