SARS-CoV-2 viral shedding in vaccinated and unvaccinated persons: A case series.

The preclinical time course of SARS-CoV-2 shedding is not well-described. Understanding this time course will help to inform risk of SARS-CoV-2 transmission. During an outbreak in a congregate setting, we collected paired mid-turbinate nasal swabs for antigen testing and reverse-transcription polymerase chain reaction (RT-PCR) every other day from all consenting infected and exposed persons. Among 12 persons tested prospectively before and during SARS-CoV-2 infection, ten of 12 participants (83%) had completed a primary COVID-19 vaccination series prior to the outbreak. We recovered SARS-CoV-2 in viral culture from 9/12 (75%) of participants. All three persons from whom we did not recover SARS-CoV-2 in viral culture had completed their primary vaccination series. We recovered SARS-CoV-2 from viral culture in 6/9 vaccinated persons and before symptom onset in 3/6 symptomatic persons. These findings underscore the need for both non-pharmaceutical interventions and vaccination to mitigate transmission.

SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge - Denver, Colorado, and San Diego, California, January-April 2021.

BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha Variant-United States, 2021.

BACKGROUND: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates. However, the impact of viral burden on these outcomes is unknown. METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 30 March 2020 to 30 April 2020 at 2 hospitals in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared characteristics and outcomes of patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with intubation and in-hospital mortality. RESULTS: We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% (Ct <25; n = 220), 17.6% (Ct 25-30; n = 216), and 6.2% (Ct >30; n = 242) with high, medium, and low viral loads, respectively (P < .001). The risk of intubation was also higher in patients with a high viral load (29.1%) compared with those with a medium (20.8%) or low viral load (14.9%; P < .001). High viral load was independently associated with mortality (adjusted odds ratio [aOR], 6.05; 95% confidence interval [CI], 2.92-12.52) and intubation (aOR, 2.73; 95% CI, 1.68-4.44). CONCLUSIONS: Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.

Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

COVID-19 Case Investigation and Contact Tracing in the US, 2020.

Importance: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19. Objective: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods. Design, Setting, and Participants: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020. Main Outcomes and Measures: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks. Results: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population. Conclusions and Relevance: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts.

Safety, tolerability, and clinical outcomes of hydroxychloroquine for hospitalized patients with coronavirus 2019 disease.

BACKGROUND: Severe acute respiratory coronavirus 2 (SARS-CoV-2) has caused a devastating worldwide pandemic. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2, but clinical data supporting HCQ for coronavirus disease 2019 (COVID-19) are limited. METHODS: This was a retrospective cohort study of hospitalized patients with COVID-19 who received ≥1 dose of HCQ at two New York City hospitals. We measured incident Grade 3 or 4 blood count and liver test abnormalities, ventricular arrhythmias, and vomiting and diarrhea within 10 days after HCQ initiation, and the proportion of patients who completed HCQ therapy. We also describe changes in Sequential Organ Failure Assessment hypoxia scores between baseline and day 10 after HCQ initiation and in-hospital mortality. RESULTS: None of the 153 hospitalized patients with COVID-19 who received HCQ developed a sustained ventricular tachyarrhythmia. Incident blood count and liver test abnormalities occurred in <15% of patients and incident vomiting or diarrhea was rare. Eighty-nine percent of patients completed their HCQ course and three patients discontinued therapy because of QT prolongation. Fifty-two percent of patients had improved hypoxia scores 10 days after starting HCQ. Thirty-one percent of patients who were receiving mechanical ventilation at the time of HCQ initiation died during their hospitalization, compared to 18% of patients who were receiving supplemental oxygen but not requiring mechanical ventilation, and 8% of patients who were not requiring supplemental oxygen. Co-administration of azithromycin was not associated with improved outcomes. CONCLUSIONS: HCQ appears to be reasonably safe and tolerable in most hospitalized patients with COVID-19. However, nearly one-half of patients did not improve with this treatment, highlighting the need to evaluate HCQ and alternate therapies in randomized trials.