Outcomes of a COVID-19 recovery program for patients hospitalized with SARS-CoV-2 infection in New York City: A prospective cohort study.

BACKGROUND: In the spring of 2020, New York City was an epicenter of coronavirus disease 2019 (COVID-19). The post-hospitalization needs of COVID-19 patients were not understood and no outpatient rehabilitation programs had been described. OBJECTIVE: To evaluate whether a virtual rehabilitation program would lead to improvements in strength and cardiopulmonary endurance when compared with no intervention in patients discharged home with persistent COVID-19 symptoms. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: Between April and July 2020, 106 patients discharged home with persistent COVID-19 symptoms were treated. Forty-four patients performed virtual physical therapy (VPT); 25 patients performed home physical therapy (HPT); 17 patients performed independent exercise program (IE); and 20 patients did not perform therapy. INTERVENTIONS: All patients were assessed by physiatry. VPT sessions were delivered via secure Health Insurance Portability and Accountability Act compliant telehealth platform 1-2 times/week. Patients were asked to follow up 2 weeks after initial evaluation. MAIN OUTCOME MEASURES: Primary study outcome measures were the change in lower body strength, measured by the 30-second sit-to-stand test; and the change in cardiopulmonary endurance, measured by the 2-minute step test. RESULTS: At the time of follow-up, 65% of patients in the VPT group and 88% of patients in the HPT group met the clinically meaningful difference for improvement in sit-to-stand scores, compared with 50% and 17% of those in the IE group and no-exercise group (P = .056). The clinically meaningful difference for improvement in the step test was met by 74% of patients in the VPT group and 50% of patients in the HPT, IE, and no-exercise groups (P = .12). CONCLUSIONS: Virtual outpatient rehabilitation for patients recovering from COVID-19 improved lower limb strength and cardiopulmonary endurance, and an HPT program improved lower limb strength. Virtual rehabilitation seems to be an efficacious method of treatment delivery for recovering COVID-19 patients.

Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter.

The widespread use of chloroquine to treat Plasmodium falciparum infections has resulted in the selection and dissemination of variant haplotypes of the primary resistance determinant PfCRT. These haplotypes have encountered drug pressure and within-host competition with wild-type drug-sensitive parasites. To examine these selective forces in vitro, we genetically engineered P. falciparum to express geographically diverse PfCRT haplotypes. Variant alleles from the Philippines (PH1 and PH2, which differ solely by the C72S mutation) both conferred a moderate gain of chloroquine resistance and a reduction in growth rates in vitro. Of the two, PH2 showed higher IC50 values, contrasting with reduced growth. Furthermore, a highly mutated pfcrt allele from Cambodia (Cam734) conferred moderate chloroquine resistance and enhanced growth rates, when tested against wild-type pfcrt in co-culture competition assays. These three alleles mediated cross-resistance to amodiaquine, an antimalarial drug widely used in Africa. Each allele, along with the globally prevalent Dd2 and 7G8 alleles, rendered parasites more susceptible to lumefantrine, the partner drug used in the leading first-line artemisinin-based combination therapy. These data reveal ongoing region-specific evolution of PfCRT that impacts drug susceptibility and relative fitness in settings of mixed infections, and raise important considerations about optimal agents to treat chloroquine-resistant malaria.