Nasal and Plasma SARS-CoV-2 RNA Levels are Associated with Timing of Symptom Resolution in the ACTIV-2 Trial of Non-hospitalized Adults with COVID-19.

Acute COVID-19 symptoms limit daily activities, but little is known about its association with SARS-CoV-2 viral burden. In this exploratory analysis of placebo recipients in the ACTIV-2/A5401 platform trial, we showed that high anterior nasal (AN) RNA levels and detectable plasma RNA were associated with delayed symptom improvement.

COVID-19 convalescent plasma therapy through the lens of the third year of the pandemic.

Serum obtained from recovered persons (convalescent serum) was the inaugural form of antimicrobial therapy for infectious diseases. Its efficacy required the administration of a sufficient amount of microbe-specific serum to mediate a biological effect early in the course of disease. Although serum therapy was discontinued when antibiotics were introduced early in the 20th century, the principles that governed its efficacy were prescient as they apply to the use of COVID-19 convalescent plasma (CCP) to treat COVID-19. Lessons learned from studies of CCP therapy for COVID-19 dating to the onset of the pandemic provide further proof of the principles of serum therapy. Analysis of these studies shows that like serum therapy, the efficacy of CCP in patients with COVID-19 depends on the administration of a high titer of SARSCoV-2 antibodies early in the course of disease.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). CONCLUSIONS: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. CLINICAL TRIALS REGISTRATION: NCT04373460.

Time to resolution of respiratory and systemic coronavirus disease 2019 symptoms in community setting.

OBJECTIVES: To assess the time to resolution of respiratory and systemic symptoms and their associated factors in outpatients during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Cohort study including adult outpatients, managed with Covidom, a telesurveillance solution, with RT-PCR-confirmed diagnosis, from 9 March 2020 until 23 February 2021. Follow up was 30 days after symptom onset. RESULTS: Among the 9667 patients included, mean age was 43.2 ± 14.0 years, and 67.5% were female (n = 6522). Median body mass index (BMI) was 25.0 kg/m2 (interquartile range 22.1-28.8 kg/m2). Main co-morbidities were: hypertension (12.9%; n = 1247), asthma (11.0%; n = 1063) and diabetes mellitus (5.5%; n = 527). The most frequent symptom during follow up was dyspnoea (65.1%; n = 6296), followed by tachypnoea (49.9%; n = 4821), shivers (45.6%; n = 4410) and fever (36.7%; n = 3550). Median times to resolution of systemic and respiratory symptoms were 3 days (95% CI 2-4 days) and 7 days (95% CI 6-8 days), respectively. Ultimately, 17.2% (95% CI 15.7%-18.8%) still presented respiratory symptoms at day 30. Longer time to respiratory symptom resolution was associated with older age, increased BMI, chronic obstructive pulmonary disease, coronary artery disease, asthma and heart failure. Regarding systemic symptoms, coronary artery disease, asthma, age above 40 years and elevated BMI were associated with longer time to resolution. CONCLUSIONS: Time to symptom resolution among outpatients with COVID-19 seemed shorter for systemic than respiratory symptoms. Prolonged respiratory symptoms were common at day 30. Risk factors associated with later resolution included age, and cardiovascular and pulmonary diseases.

Persistent COVID-19 Symptoms Minimally Impact the Development of SARS-CoV-2-Specific T Cell Immunity.

SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed SARS-CoV-2-specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms or symptoms persisting for 18 days or more. We observed that persistent COVID-19 symptoms were not associated with the development of an overtly dysregulated cellular immune response. Furthermore, we observed that reactivity against the N protein from SARS-CoV-2 correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide insight into the processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.

Clinical and epidemiological data of COVID-19 from Regensburg, Germany: a retrospective analysis of 1084 consecutive cases.

BACKGROUND: COVID-19 is a syndrome caused by the recently emerged SARS-CoV-2. We collected clinical and epidemiologic data in an almost complete cohort of SARS-CoV-2 positive individuals from Regensburg, Germany, from March 2020 to May 2020. METHODS: Analysis of a retrospectively documented cohort of consecutive COVID-19 cases recorded between March 7, 2020 and May 24, 2020 as part of an infection control investigation program, with prospective follow-up interviews gathering information on type and duration of symptoms and COVID-19 risk factors until June 26, 2020. RESULTS: Of 1089 total cases, 1084 (99.5%) cases were included. The incidence during the time period was 315.4/100,000, lower than in the superordinate government district Oberpfalz (468.5/100,000) and the overall state of Bavaria (359.7/100,000). The case fatality ratio (CFR) was 2.1%. Among fatal cases, the mean age was 74.4 years and 87% presented with known risk factors, most commonly chronic heart disease, chronic lung disease, kidney disease, and diabetes mellitus. 897 cases (82.7%) showed at least one symptom, most frequently cough (45%) and fever (41%). Further, 18% of cases suffered from odour/taste disorder. 17% of total cases reported no symptoms. The median duration of general illness was 10 days. During follow-up, 8.9% of 419 interviewed cases reported at least one symptom lasting at least 6 weeks, and fatigue was the most frequent persistent symptom. DISCUSSION: We report data on type and duration of symptoms, and clinical severity of nearly all (99.5%) patients with SARS-CoV-2 recorded from March 2020 to May 2020 in Regensburg. A broad range of symptoms and symptom duration was seen, some of them lasting several weeks in a considerable number of cases. The case-fatality ratio was 2.1%. Asymptomatic cases may be underrepresented due to the nature of the study.

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.

Symptom Profiles and Progression in Hospitalized and Nonhospitalized Patients with Coronavirus Disease, Colorado, USA, 2020.

To improve recognition of coronavirus disease (COVID-19) and inform clinical and public health guidance, we randomly selected 600 COVID-19 case-patients in Colorado. A telephone questionnaire captured symptoms experienced, when symptoms occurred, and how long each lasted. Among 128 hospitalized patients, commonly reported symptoms included fever (84%), fatigue (83%), cough (73%), and dyspnea (72%). Among 236 nonhospitalized patients, commonly reported symptoms included fatigue (90%), fever (83%), cough (83%), and myalgia (74%). The most commonly reported initial symptoms were cough (21%-25%) and fever (20%-25%). In multivariable analysis, vomiting, dyspnea, altered mental status, dehydration, and wheezing were significantly associated with hospitalization, whereas rhinorrhea, headache, sore throat, and anosmia or ageusia were significantly associated with nonhospitalization. General symptoms and upper respiratory symptoms occurred earlier in disease, and anosmia, ageusia, lower respiratory symptoms, and gastrointestinal symptoms occurred later. Symptoms should be considered alongside other epidemiologic factors in clinical and public health decisions regarding potential COVID-19 cases.

Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production.

Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19. Antibody responses to SARS-CoV-2 are unimodally distributed over a broad range, with symptom severity correlating directly with virus-specific antibody magnitude. Seventy-six subjects followed longitudinally to ∼100 days demonstrated marked heterogeneity in antibody duration dynamics. Virus-specific IgG decayed substantially in most individuals, whereas a distinct subset had stable or increasing antibody levels in the same time frame despite similar initial antibody magnitudes. These individuals with increasing responses recovered rapidly from symptomatic COVID-19 disease, harbored increased somatic mutations in virus-specific memory B cell antibody genes, and had persistent higher frequencies of previously activated CD4+ T cells. These findings illuminate an efficient immune phenotype that connects symptom clearance speed to differential antibody durability dynamics.

The relationship between diagnostic value of chest computed tomography imaging and symptom duration in COVID infection.

OBJECTIVES: Severe acute respiratory syndrome-coronovirus-2 is a global public health problem, in which early diagnosis is required to prevent the spread of infection. In this study, we aimed to reveal the diagnostic value of chest computed tomography (CT) imaging with respect to symptom duration. METHODS: This retrospective study involved patients from five centers, who were admitted with typical COVID-19 symptoms and found to be positive for COVID-19 real-time reverse transcription-polymerase chain reaction (rtRT-PCR) test. RESULTS: One hundred and five patients with positive COVID-19 rtRT-PCR test were involved in the study. Sixty percent of these patients had chest CT imaging findings consistent with COVID-19 pneumonia. The most common chest CT finding was bilateral and subpleural ground-glass opacity in middle-lower lobes of the lungs. Chest CT findings were detected in 85.1% of the patients with a symptom duration of more than 2 days. In receiver operating characteristic analysis of this parameter, area under the curve (AUC) was 0.869, while sensitivity and specificity were 90.5% and 76.2%, respectively. It was notable that chest CT findings were 7.17 times more common among the patients aged 60 years and older, with AUC, specificity, and positive predictive value of 0.768, 88.1%, and 84.8%, respectively. CONCLUSION: Chest CT imaging is a quite valuable tool in patients with longer than 2 days' duration of symptoms, in whom clinical and epidemiological data support the diagnosis of COVID-19 infection. We suggest that the diagnosis of COVID-19 pneumonia should be made with chest CT imaging when rtRT-PCR test cannot be performed or gives a negative result, which is important for public health and to prevent the spread of infection.