Days Of Viral Shedding Research Articles

Trajectory of Viral RNA Load Among Persons With Incident SARS-CoV-2 G614 Infection (Wuhan Strain) in Association With COVID-19 Symptom Onset and Severity

The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development. To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity. This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days. Laboratory-confirmed SARS-CoV-2 infection. The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity. A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2-positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain). This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.

Administration of HeberFERON in Patients with Persistent Oropharyngeal SARS-CoV-2 Wuhan/D614G Strain Viral Shedding

Study background: HeberFERON accelerates SARS-CoV-2 clearance in COVID-19 cases. Considering this we evaluated the employment of HeberFERON in patients with more than 14 days of viral shedding. Methods: This is a case series study of mild or moderate ill patients with laboratory-confirmed SARS-CoV-2 from one hospital in Havana, Cuba. We evaluated the effect and safety of HeberFERON in patients previously treated with Heberon Apha R that resulted with prolonged viral shedding. All patients received lopinavir-ritonavir 200/50 mg every 12 h and chloroquine 250 mg every 12 h. The primary endpoint was the time to negativization of viral RNA in patients with persistent viral shedding. The protocol was approved by the Ethics Committee of the Luis Diaz Soto Hospital. Results: The characteristics of the individuals included the age ranged from 19-87 years with a mean of 40 years, (Study and Control I groups), while in the Control group II the mean age was 43.8 years. Leukocytes, platelets, neutrophils, and eosinophils, show a significantly lower counts in the groups with viral persistence. Under IFN treatment the median viral shedding duration from diagnosis were 21 days and 19 days in Study group and Control group II, respectively. The Control group I showed a median viral shedding of 11 days (log-rank p = 0.000). Significant longer median viral negativization time (19 days) of symptomatic than asymptomatic patients (11 days, Long-rank p = 0.004), was observed. In patients under Heberon Alpha R treatment that resulted persistent for viral presence, the median time to viral negativization was 7 days for the period of administration of HeberFERON. Being symptomatic at diagnosis was significantly associated with viral persistence. The HeberFERON showed an adequate safety profile. Conclusion: HeberFERON showed a safe and rapid negativization of patients with viral persistence, achieving negativization in more than 50% of patients in 7 days.

Characteristics of Viral Shedding in Respiratory Samples and Specific Antibodies Production in 564 COVID-19 Patients.

SummaryPositive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including “early diagnosis and early treatment”. This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65–5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Association between Early Treatment and Favorable Clinical Outcomes of COVID-19: Evidence from Nine Provinces in China

Background: Few studies have examined the association between treatment given time and clinical outcomes, which is indeed of great importance to clinical management of coronavirus disease 2019 (COVID-19). We performed this study to explore whether early treatment brings favorable clinical outcomes. Methods: In this retrospective multicenter study, we included patients aged 18 to 87 years with confirmed COVID-19 on admission from 54 hospitals in nine provinces of China from 21 January to 10 March, 2020. Final date of follow-up was March 17, 2020. All patients were treated by Lung cleansing & detoxifying decoction combined with western medicine. Patients were divided into four groups according to the interval from the first date of onset of symptoms to the date of starting a treatment, i.e., ≤1 week group (≤7 days), 1-2 weeks group (>7 days and ≤14 days), 2-3 weeks group (>14 days and ≤21 days) and >3 weeks group (>21 days). Multivariable Cox proportional hazard ratio (HR) models were used to estimate unadjusted and adjusted HRs and 95% confidence intervals (CIs) for the association between the treatment given time and clinical outcomes (time to recovery, days of viral shedding, duration of hospital stay, course of disease, fever and CT images). Findings: Of the 782 patients (median age was 46 years old, and 405 (52%) were male), there were 321 (41%) patients in ≤1 week group, 221 (28%) in 1-2 weeks group, 123 (16%) in 2-3 weeks group and 117 (15%) in >3 weeks group. Compared to patients in later treatment group (greater than 3 weeks), patients in earlier treatment groups of less than 1 week, 1 to 2 weeks, or 2 to 3 weeks had higher likelihood of recovery, with adjusted HR (95% CI) of 3.81 (2.65-5.48), 2.63 (1.86-3.73) and 1.92 (1.34-2.75), respectively. The median days of viral shedding was 13 days and 12 days in 2-3 weeks group and 3 weeks group (P=0.0137). The median course of disease decreased from 34 days to 24 days, 21 days and 18 days when treatment was given every one week in advance compared to that was given later than 3 weeks from the onset of symptoms (P<0.0001). Treatment within 1 week since onset of symptoms was related with a decrease of 1 to 4 days in terms of median duration of hospital stay compared to later treatment (P<0.0001). Interpretation: Earlier treatment was associated with favorable outcomes, including sooner recovery, shorter time to viral shedding, and shorter duration of hospital stay. This paper demonstrated that early treatment could be an effective strategy in the epidemic control, and can provide evidence for government and international organizations to develop the policy of COVID-19. Funding Statement: This study was supported by “National Science and Technology Major Project” (2018ZX10101001-005-003, 2018ZX10101001-005-004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by National Administration of Traditional Chinese Medicine, Administration of Traditional Chinese Medicine of nine provinces and the institutional board of 54 participating setting. Due to the urgency of the treatment of COVID-19, the requirement for informed consent from study participants was replaced by verbal consent.

Clinical characteristics of patients with COVID-19 presenting with gastrointestinal symptoms as initial symptoms: Retrospective case series.

BACKGROUNDA large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms.AIMTo characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms.METHODSThis is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis.RESULTSAmong the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01).CONCLUSIONCOVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

Clinical Features of Severe Influenza A (H1N1) Virus Infection

ObjectiveTo highlight the clinical presentations of influenza A (H1N1) infection, for early diagnosis and recognition by the pediatricians.MethodsIn this retrospective study, the medical records of inpatients with influenza A (H1N1) infection between November 1, 2009 and May 31, 2011were reviewed.ResultsEighty pediatric in-patients with median age 41.9 mo were studied. ARDS (11/80), pneumothorax (8/80), pleural effusion (7/80) and encephalopathy (7/80) were the most frequent complications. Six of 11 ARDS patients died;all of them were under 5 y. The median days of viral shedding was 11.4 d. Slight increase of Il-6, Il-10 and TNF-γ were revealed in some cases.ConclusionsDuring late stage of pandemic wave, the majority of patients were young children. Children with severe Influenza A (H1N1) are prone to develop complications, and die from ARDS. If influenza-like illness is accompanied by neurologic signs, influenza A (H1N1) virus infection should be considered. The viral shedding in children is longer than in adults.

Duration of viral shedding in hospitalized patients infected with pandemic H1N1

BackgroundThe first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm.MethodsAn observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information.ResultsEleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding.ConclusionsOur results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.

A Mouse Model of Picornavirus-induced Airway Infection and Inflammation

RATIONALE: Rhinoviruses, which are members of the picornavirus family, are important causes of asthma exacerbations and early life wheezing illnesses that are associated with increased asthma risk. Given the absence of natural rhinovirus infections in rodents, we used attenuated mengovirus, a picornavirus whose wild-type form causes systemic infections in its natural murine hosts, to induce respiratory infections in mice, which we hypothesized would serve as a useful model for neutrophilic inflammatory processes in human rhinovirus infections. METHODS: BALB/c mice received intranasal inoculations with active or UV-inactivated attenuated mengovirus or vehicle. On various days postinoculation, inflammatory cells and mediators were assessed in the bronchoalveolar lavage (BAL) fluid and lung tissue, and pulmonary function was measured. RESULTS: Mice inoculated with attenuated mengovirus, compared with those inoculated with vehicle or UV-inactivated virus, shed infectious virus for 5 days, had peribronchiolar, perivascular, and alveolar cellular infiltrates, had significantly elevated (p < 0.05) levels of BAL neutrophils, neutrophil chemoattractant CXCR2 ligands (CXCL1, CXCL2, CXCL5), other chemokines/cytokines upregulated during rhinovirus infections (CXCL10, CCL2, and interferon-α, -β, and -λ), and exhibited significant increases (p < 0.05) in BAL fluid myeloperoxidase levels and wet-dry lung weight ratios, indicating neutrophil activation and airway injury, respectively. In these healthy mice, there were no virus-related changes in pulmonary function, consistent with experimental rhinovirus inoculations in healthy humans. CONCLUSIONS: Attenuated mengovirus caused respiratory infections in mice with several days of viral shedding accompanied by lower airway neutrophilic inflammation. These features suggest that this model will be useful for defining mechanisms of rhinovirus-induced airway inflammation in humans.

A rat model of picornavirus-induced airway infection and inflammation

BackgroundInfection of the lower airways by rhinovirus, a member of the picornavirus family, is an important cause of wheezing illnesses in infants, and plays an important role in the pathogenesis of rhinovirus-induced asthma exacerbations. Given the absence of natural rhinovirus infections in rodents, we investigated whether an attenuated form of mengovirus, a picornavirus whose wild-type form causes systemic rather than respiratory infections in its natural rodent hosts, could induce airway infections in rats with inflammatory responses similar to those in human rhinovirus infections.ResultsAfter inoculation with 107 plaque-forming units of attenuated mengovirus through an inhalation route, infectious mengovirus was consistently recovered on days 1 and 3 postinoculation from left lung homogenates (median Log10 plaque-forming units = 6.0 and 4.8, respectively) and right lung bronchoalveolar lavage fluid (median Log10 plaque-forming units = 5.8 and 4.0, respectively). Insufflation of attenuated mengovirus, but not vehicle or UV-inactivated virus, into the lungs of BN rats caused significant increases (P < 0.05) in lower airway neutrophils and lymphocytes in the bronchoalveolar lavage fluid and patchy peribronchiolar, perivascular, and alveolar cellular infiltrates in lung tissue sections. In addition, infection with attenuated mengovirus significantly increased (P < 0.05) lower airway levels of neutrophil chemoattractant CXCR2 ligands [cytokine-induced neutrophil chemoattractant-1 (CINC-1; CXCL1) and macrophage inflammatory protein-2 (MIP-2; CXCL2)] and monocyte chemoattractant protein-1 (MCP-1; CCL2) in comparison to inoculation with vehicle or UV-inactivated virus.ConclusionAttenuated mengovirus caused a respiratory infection in rats with several days of viral shedding accompanied by a lower airway inflammatory response consisting of neutrophils and lymphocytes. These features suggest that mengovirus-induced airway infection in rodents could be a useful model to define mechanisms of rhinovirus-induced airway inflammation in humans.

Un modèle épidémiologique de l’herpès génital pour l’évaluation des interventions thérapeutiques et prophylactiques: Application à la France

This study was performed to quantify the development of the number of cases of genital herpes and to assess the impact of different treatment strategies in France. A model for the natural history of herpes simplex virus genital infection is presented and applied to the French population. The model encompasses infection by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), first episodes, recurrences, viral shedding and the effect of treatment on infected individuals. In the Year 2000, 270,000 individuals would have suffered from genital herpes in France. A total annual cumulated number of 1.5 million episodes of recurrence and 23 million days of viral shedding were estimated. Seventy percent of viral shedding occurred in sub-clinical seropositive individuals. The expected number of attributable neonatal deaths remained very low. Systematic treatment of clinical episodes might reduce the number of days with lesions (- 27 p. 100), and is also effective on viral shedding (symptomatic: - 50 p. 100). Continuous treatment of the most severe patients (>or=6 recurrences per Year) might reduce viral shedding slightly more (- 85 p. 100). Antiviral treatment might have a major impact on the quality of life of these patients but would only slightly curb the number of new infections. This model tries to integrate the various data currently available at international level on the epidemiology of genital herpes. However, many aspects are still not well documented and remain uncertain. It is therefore necessary to define various assumptions in order to simulate the natural history of the disease in a population. The lack of French data especially on the HSV-1 and HSV-2 seroprevalence profiles reinforces these uncertainties. Our results should hence be considered as exploratory. However, this modeling approach is the only possible way to integrate the multiple parameters describing the pathology and predicting of the public health impact of different interventions. This model is an open tool which may be modified when new data become available.

Evaluation of Cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zeland rabbit ocular model

The antiviral inhibitory activity of Cidofovir [1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate, HPMPC, GS-504] against adenovirus type 5 (Ad5) in the New Zealand rabbit ocular replication model was evaluated. The 50% inhibitory dose (ID50) of Cidofovir was determined to be 4.7–9.5 μg/ml against four adenoviruses (two Ad5, Ad8 and Ad14) by plaque reduction assay in A549 cells. Twenty-four New Zealand rabbits received intrastromal inoculation and topical application of 2 × 106 plaque-forming units (PFU) per eye of Ad5 McEwen, a clinical isolate. Cidofovir was administered topically at three different concentrations twice per day, beginning 16 h postinoculation and continuing for 20 consecutive days. The inhibitory effects were determined by measuring suppression of virus replication and by observation of the clinical effects. Compared to the placebo group, the 1% and 0.5% Cidofovir-treated groups showed significantly reduced Ad5 ocular titers, fewer days of viral shedding and less severe showed significantly reduced Ad5 ocular titers, fewer days of viral shedding and less severe subepithelial opacities (P = 0.0001). The 1% Cidofovir group had the lowest humoral antibody titer against adenovirus antigens, but the difference was not significant (P = 0.24). Cidofovir proved to have potent antiviral activity against adenovirus replication and may have great promise for the treatment of adenovirus infection. Further investigation is recommended.

Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans

The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both groups), days of viral shedding (3.1 +/- 1.3 for the LY217896 group; 2.8 +/- 1.3 for the placebo group), and titers of virus in nasal washings did not differ between the groups. Mild upper respiratory tract illness (72% in the LY217896 group; 69% in the placebo group) developed in similar proportions of each group. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection.

Colostrum

Despite increasing awareness of the importance of passive immunity in calves to reduce disease prevalence, morbidity from calfhood diseases, days to first illness, sick days, days of viral shedding, viremia, growth and productivity(l-6), 20 to 30% of neonates will be hypo- or agammaglobulinemic. Failure of passive transfer of maternal immunoglobulins (FPT) occurs when there is a problem with 1 or more of the 3 phases of passive transfer: formation of colostrum with a high concentration of immunoglobulin, ingestion of an adequate volume of colostrum by the calf in a timely fashion, or efficient absorption of colostral immunoglobulin. Some calves with FPT are healthy and productive neonates, which is a reflection of the importance of other factors including environmental conditions, management practices, pathogen load, pathogen virulence, and nutrition of the calf in addition to acquisition of passive immunity. There is general acceptance that failure of passive transfer exists when calves between 36 and 48 hours of age have serum immunoglobulin concentrations less than 1000 mg/di. Individual calf problems can occur when its serum immunoglobulin concentration is below 1000 mg/di; herd problems occur with increased prevalence of scours and respiratory disease occur when large numbers of calves have FPT.

Oral acyclovir in the treatment of genital herpes: Preliminary report of a multicenter trial

Ninety patients with genital herpes (29 initial and 61 recurrent episodes) were entered into a double-blind randomized trial of oral acyclovir and placebo. Treatment consisted of 200 mg acyclovir five times a day for five days or matching placebo. Therapy was initiated a mean of 2.8 days and 1.0 days after onset of lesions in initial and recurrent infections respectively. The 13 culture-positive patients with initial disease who received acyclovir had a shorter median duration in days of viral shedding (1.0), pain (3.5), combined symptoms (3.5), time to crusting (3.5), and time to complete healing (5.5) than the 11 culture-positive placebo recipients whose scores were 8.0, 4.5, 4.5, 9.0, and 11.0 respectively (p < 0.05 for all comparisons). Patients with recurrent disease receiving acyclovir also experienced a reduction in the median duration in days of viral shedding (0.5), time to crusting (men only) (3.0), and time to complete healing (5.0), compared with 2.5, 4.0, and 7.0 days, respectively, for control patients (p < 0.01 for each variable). New lesion formation was effectively prevented by acyclovir in patients with both initial and recurrent infections (p < 0.05). Oral acyclovir therapy was well-tolerated and shortened the course of both initial and recurrent genital herpes.