Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

IDSA Guideline on the Treatment and Management of COVID-19 with Famotidine
These randomized controlled trials (RCTs) compared treatment with famotidine against no famotidine among ambulatory persons with COVID-19 and persons hospitalized with severe COVID-19. Symptom resolution in ambulatory patients at day 28 failed to show or to exclude a beneficial effect of high-dose famotidine (risk ratio [RR]: 1.1, 95% confidence interval [CI]: 0.76, 1.58 – not directly reported but estimated from the survival curve; low certainty of evidence [CoE]). Hospitalized patients with severe disease In hospitalized patients with severe COVID-19, famotidine at standard dose failed to show or exclude a beneficial effect on mortality, need for mechanical ventilation, or need for ICU care (RR: 0.89, 95% CI: 0.36, 2.2; RR: 0.88, 95% CI: 0.53, 1.45; RR: 0.9, 95% CI: 0.51, 1.58, respectively; all low CoE). Time to symptom resolution was shorter in the famotidine group (mean difference [MD] -0.9 days, 95% CI: -1.44, -0.36), as was length of hospital stay (MD -1.7 days, 95% CI: -2.77, -1.13), although due to lack of blinding these estimates remain less certain (low CoE). Based off these results, among ambulatory patients with mild-to-moderate COVID-19, the IDSA panel suggests against famotidine for the treatment of COVID-19 (Conditional recommendation, low certainty of evidence). Among hospitalized patients with severe COVID- 19, the IDSA panel suggests against famotidine for the treatment of COVID-19. (Conditional recommendation, low certainty of evidence)
Children and COVID-19: State level Data Report
A joint report from the American Academy of Pediatrics and the Children’s Hospital Association. Summary of publicly reported data from 49 states, NYC, DC, PR, and GU Version: 5/26/22. The numbers in this report represent cumulative counts since states began reporting. The data are based on how public agencies collect, categorize and post information. All data reported by state/local health departments are preliminary and subject to change and reporting may change over time. Notably, in the summer of 2021 and winter of 2022, some states have revised cases counts previously reported, begun reporting less frequently, or dropped metrics previously reported. For example, due to several changes on their dashboards and the data currently available, AL, TX, HI, DC and MS data in this report are not current (cumulative data through 7/29/21, 8/26/21, 1/13/22, 3/3/22, and 3/10/22 respectively). Readers should consider these factors. States may have additional information on their web sites.
Duration of viable virus shedding in SARS-CoV-2 omicron variant infection
In this longitudinal cohort of individuals with symptomatic, non-severe COVID-19 infection, we found no difference in viral kinetics between omicron variant infection and delta variant infection or by prior vaccination history. Over 50% of individuals had replication competent, culturable virus at day 5, and 25% had culturable virus at day 8. Our cohort is limited to individuals with symptomatic, non-severe COVID-19 disease. A greater proportion of individuals infected with omicron had received their booster vaccine, although vaccination status was not associated with viral decay kinetics in multivariable models. Additional studies are needed to correlate viral culture positivity with confirmed transmission and to validate the utility of clinical antigen testing for defining optimal isolation periods.
The association between pre-exposure to glucocorticoids and other immunosuppressant drugs with severe COVID-19 outcomes
Whether pre-infection use of immunosuppressant drugs is associated with COVID-19 severity remains unclear. The study was aimed to determine the association between pre-infection use of immunosuppressant drugs with COVID-19 outcomes within one month. This cohort study included ≥18 years-old individuals with underlying conditions associated with an immunocompromised state and diagnosed with COVID-19 between February-2020 and January-2021 at Karolinska University Hospital, Stockholm. Exposure to immunosuppressant drugs was defined based on dose and duration of drugs (glucocorticoids, and drugs included in L01 or L04 chapter of ATC-classification) before COVID-19 diagnosis. Outcomes included hospital admission, ICU admission, mechanical ventilation, mortality, renal failure, stroke, pulmonary embolism, and cardiac event. Odds ratios(OR) were calculated using logistic regression and baseline covariate adjustment for confounding with inverse probability of treatment weights. Of 1067 included individuals, 444 were pre-exposed to immunosuppressive treatments before COVID-19 diagnosis (72 high-dose glucocorticoids, 255 L01 drugs(antineoplastics), 198 L04(other immunosuppressants) and 78 to multiple drugs). There was no association between pre-exposure and hospital admission (OR 0.83,[95%CI 0.64-1.09]) due to COVID-19. Pre-exposure to L01 or L04 drugs were not associated with hospital admission (aORs: 1.23[0.86-1.76] and 1.31[0.77-2.21) or other outcomes. High-dose glucocorticoids (≥20mg/day prednisolone equivalent) were associated with hospital admission (aOR 2.50[1.26-4.96]), cardiac events (aOR 1.93,[1.08-3.46]),pulmonary embolism (aOR 2.78[1.08-7.15]) and mortality (aOR 3.48,[1.77-6.86]) due to COVID-19. Antineoplastic and other immunosuppressants drugs were not associated with COVID-19 severity whereas high-dose glucocorticoids were associated. Further studies should evaluate the effect of pre-exposure of different dose of glucocorticoids on COVID-19 prognosis.
Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs
RECOVER researchers hypothesized that consistent subgroups of patients with long COVID can be defined based on the spectrum of phenotypic features in the patients’ electronic health records (EHR). They ultimately found 6 clusters or 6 subgroups.
Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic
Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2–69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had “low risk of bias”, and three were in the “some concerns” category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.

Antiviral Therapeutics and Vaccines

Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data
This was a retrospective cohort study with propensity matching and difference-in-difference analyses done in the U.S. (VA) healthcare system. Participants were veterans age ≥18 years as of January 1, 2022, receiving VA healthcare. Researchers compared a cohort of 1,848 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to matched controls selected from 251,756 patients who were on immunocompromised or otherwise at high risk for COVID-19. Compared to propensity-matched controls, tixagevimab/cilgavimab-treated patients (those that got EvuSheld) had a lower incidence of the composite COVID-19 outcome (17/1733 [1.0%] vs 206/6354 [3.2%]; HR 0.31; 95%CI, 0.18-0.53), and individually SARS-CoV-2 infection (HR 0.34; 95%CI, 0.13-0.87), COVID-19 hospitalization (HR 0.13; 95%CI, 0.02-0.99), and all-cause mortality (HR 0.36; 95%CI, 0.18-0.73)
Efficacy of anti-SARS-CoV-2 monoclonal antibodies prophylaxis and vaccination on Omicron COVID-19 in kidney transplant recipients
In this study, outcomes were studied according to immunization status, as described in Figure 1, as follows, group 1: vaccine-induced immunization, 288 patients; group 2: passive immunization with tixagevimab/cilgavimab, 412 patients. In this group, 267 KTRs received casirivimab-imdevimab as a first step of protection before receiving tixagevimab/cilgavimab. All KTRs of group 2 received 2 i.m. injections of 150 mg tixagevimab þ 150 mg cilgavimab between December 23, 2021 and February 7, 2022; and group 3: insufficient immunization, 160 patients. In this group, 62 received casirivimab-imdevimab. During follow-up, 113 patients (13.1%) presented an Omicron infection, of which 85 were symptomatic (from December 23, 2021 to February 14, 2022—103 cases of infection [91.2%]; from February 14, 2022 to March 7, Q5 2022—10 cases of infection [8.8%]). Twenty-one patients required hospitalization, including 8 in the intensive care unit. Five patients died of COVID-19. The occurrence of infection, symptomatic infection, hospitalization, intensive care unit hospitalization, and COVID-19 death were significantly increased in patients in group 3. Patients who received passive immunization with tixagevimab/cilgavimab had outcomes similar to those of patients with vaccine-induced immunization, but they had significantly fewer infections (both severe and nonsevere), compared to KTRs considered unprotected. Despite its potential bias, per the retrospective design, to our knowledge, this study shows for the first time the potential clinical usefulness of mAbs against Omicron in KTRs with weak or no response to vaccine, as a prophylaxis strategy. These results challenge the reduced efficacy of mAbs that has been shown in vitro. No serious adverse event was reported in our cohort who received tixagevimab/cilgavimab. Multicentric prospective or retrospective studies are needed to confirm these encouraging results for the protection of immunosuppressed patients against COVID-19.
Virologic characterization of symptom rebound following nirmatrelvir-ritonavir treatment for COVID-19
Researchers enrolled seven individuals with recurrent symptoms following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected at enrollment and for a median of 17 days after initial diagnosis. Three of seven had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were identified.

Diagnostics

COVID-19 symptoms and duration of direct antigen test positivity at a community testing and surveillance site, January 2021-2022
In this community-based surveillance study, researchers detected differences in symptomatology between the Omicron period and prior variant-periods, and by age and vaccination status. Five days after symptom onset, 80% remained positive with a BinaxNOW test. During the Omicron period, differences in symptomatology may be due to rising population immunity and a new variant. BinaxNOW positivity remained high among re-testers, which supports guidelines that use rapid tests to shorten the isolation period.

Epidemiology

Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study
In January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. Researchers conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4–6 compared to culture. Among 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively. The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. Researchers found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.
Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms
There are the results of a cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and pre-pandemic control groups were included. Forty-four patients and 10 healthy controls, and 41 patient controls (COVID negative without evidence of CNS infection) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r = 0.38;P = .03) and interferon γ (r = 0.42; P = .01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β₂-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P = .03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P = .04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P = .002). In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
Transmission Dynamics of COVID-19 in Ghana and the Impact of Public Health Interventions
This study characterized COVID-19 transmission in Ghana in 2020 and 2021 by estimating the time-varying reproduction number (Rt) and exploring its association with various public health interventions at the national and regional levels. Ghana experienced four pandemic waves, with epidemic peaks in July 2020 and January, August, and December 2021. The epidemic peak was the highest nationwide in December 2021 with Rt>2.Throughout 2020 and 2021, per-capita cumulative case count by region increased with population size. Mobility data suggested a negative correlation between Rt and staying home during the first 90 days of the pandemic. The relaxation of movement restrictions and religious gatherings was not associated with increased Rt in the regions with fewer case burdens. Rt decreased from >1. When schools reopened in January 2021 to <1 after vaccination rollout in March 2021. Findings indicated most public health interventions were associated with Rt reduction at the national and regional levels.