Patients ask me if they come down with Covid-19, what am I going to give them? I point out that 80% of patients have mild disease and require no treatment. They also ask if there is something that they can take that will prevent them from getting severe disease. The answer to the latter is “No”…. for now. There is a new study that was published last week that showed that infusing viral antibodies could reduce the viral load and possibly shorten the duration of symptoms. The first article is an excerpt form last week’s New England Journal article on Mild or Moderate Covid-19 followed by the article on the antibody infusions. And hydroxychloroquine still doesn’t work.
MANAGEMENT OF COVID-19
Patients who have mild illness usually recover at home, with supportive care and isolation. It may be useful for people who are at high risk for complications to have a pulse oximeter to self-monitor the oxygen saturation.
Patients who have moderate disease should be monitored closely and sometimes hospitalized; those with severe disease should be hospitalized. If there is clinical evidence of bacterial pneumonia, empirical antibacterial therapy is reasonable but should be stopped as soon as possible. Empirical treatment for influenza may be considered when seasonal influenza transmission is occurring until results of specific testing are known.
Treatment of Covid-19 depends on the stage and severity of disease (Figure 1).41 Because SARS-CoV-2 replication is greatest just before or soon after symptom onset, antiviral medications (e.g., remdesivir and antibody-based treatments) are likely to be most effective when used early. Later in the disease, a hyperinflammatory state and coagulopathy are thought to lead to clinical complications; in this stage, antiinflammatory medications, immunomodulators, anticoagulants, or a combination of these treatments may be more effective than antiviral agents. There are no approved treatments for Covid-19 but some medications have been shown to be beneficial.
Hydroxychloroquine and Chloroquine with or without Azithromycin
Chloroquine and hydroxychloroquine have in vitro activity against SARS-CoV-2, perhaps by blocking endosomal transport.44 Results from single-group observational studies and small randomized trials led to initial interest in hydroxychloroquine for the treatment of Covid-19, but subsequent randomized trials did not show a benefit. The Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial showed that, as compared with standard care, hydroxychloroquine did not decrease mortality among hospitalized patients.45 In another randomized trial involving hospitalized patients with mild-to-moderate Covid-19, hydroxychloroquine with or without azithromycin did not improve clinical outcomes.46 Moreover, no benefit was observed with hydroxychloroquine in randomized trials involving outpatients with Covid-1947,48 or patients who had recent exposure to SARS-CoV-2 (with hydroxychloroquine used as postexposure prophylaxis).49,50 Current guidelines recommend that hydroxychloroquine not be used outside clinical trials for the treatment of patients with Covid-19.51,52
Remdesivir, an inhibitor of RNA-dependent RNA polymerase, has activity against SARS-CoV-2 in vitro53 and in animals.54 In the final report of the Adaptive Covid-19 Treatment Trial 1 (ACTT-1),55 which involved hospitalized patients with evidence of lower respiratory tract infection, those randomly assigned to receive 10 days of intravenous remdesivir recovered more rapidly than those assigned to receive placebo (median recovery time, 10 vs. 15 days); mortality estimates by day 29 were 11.4% and 15.2%, respectively (hazard ratio, 0.73; 95% confidence interval, 0.52 to 1.03). In another trial, clinical outcomes with 5 days of remdesivir were similar to those with 10 days of remdesivir.56 In an open-label, randomized trial involving hospitalized patients with moderate Covid-19 (with pulmonary infiltrates and an oxygen saturation of ≥94%), clinical status was better with 5 days of remdesivir (but not with 10 days of remdesivir) than with standard care, but the benefit was small and of uncertain clinical importance.57 The FDA has issued an EUA for remdesivir for hospitalized patients with Covid-19.58 Guidelines recommend remdesivir for the treatment of hospitalized patients with severe Covid-19 but consider data to be insufficient to recommend for or against the routine use of this drug for moderate disease.51,52 Decisions about the use of remdesivir in hospitalized patients with moderate disease should be individualized and based on judgment regarding the risk of clinical deterioration.
Convalescent Plasma and Monoclonal Antibodies
Small randomized trials of convalescent plasma obtained from people who have recovered from Covid-19 have not shown a clear benefit.59 Data from patients with Covid-19 who were enrolled in a large expanded-access program for convalescent plasma in the United States suggested that mortality might be lower with receipt of plasma with a high titer of antibody than with receipt of plasma with a low titer of antibody; the data also suggested that mortality might be lower when plasma is given within 3 days after diagnosis than when plasma is given more than 3 days after diagnosis.60,61 Interpretation of these data is complicated by the lack of an untreated control group and the possibility of confounding or a deleterious effect of receiving plasma with a low titer of antibody. The National Institutes of Health Covid-19 Treatment Guidelines Panel51 and the FDA, which issued an EUA for convalescent plasma in August 2020,60 emphasize that convalescent plasma is not the standard of care for the treatment of Covid-19. Ongoing randomized trials must be completed to determine the role of convalescent plasma.
Monoclonal antibodies directed against the SARS-CoV-2 spike protein are being evaluated in randomized trials as treatment for people with mild or moderate Covid-19 and as prophylaxis for household contacts of persons with Covid-19. Published data are not yet available to inform clinical practice.
Because of concerns that a hyperinflammatory state may drive severe manifestations of Covid-19, immunomodulating therapies have been or are being investigated. In the RECOVERY trial, dexamethasone reduced mortality among hospitalized patients with Covid-19, but the benefit was limited to patients who received supplemental oxygen and was greatest among patients who underwent mechanical ventilation.62 Dexamethasone did not improve outcomes, and may have caused harm, among patients who did not receive supplemental oxygen, and thus it is not recommended for the treatment of mild or moderate Covid-19.
USE OF CONCOMITANT MEDICATIONS IN PEOPLE WITH COVID-19
Because SARS-CoV-2 enters human cells through the ACE2 receptor,3 questions were raised regarding whether the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) — which may increase ACE2 levels — might affect the course of Covid-19.63 However, large observational studies have not shown an association with increased risk,64 and patients who are receiving ACE inhibitors or ARBs for another indication should not stop taking these agents, even if they have Covid-19.63,65 In addition, several authoritative organizations have noted the absence of clinical data to support a potential concern about the use of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with Covid-19,66 and results from a cohort study were reassuring.67
Here is a summary from the article in the New England Journal of Medicine:
Antibody treatment: An investigational neutralizing antibody treatment shows some promise for outpatients with mild-to-moderate COVID-19, according to an interim analysis from an industry-supported, phase 2 trial in the New England Journal of Medicine. The monoclonal antibody, known as LY-CoV555, was derived from convalescent plasma from a COVID-19 patient. In the trial, some 450 patients were randomized to a single infusion of LY-CoV555 (at one of three doses) or placebo over 1 hour. By day 11, viral load — the primary outcome — had decreased in all groups, but the difference between LY-CoV555 and placebo was significant only for the middle dose. Of note, patient symptoms were less severe with LY-CoV555 than with placebo from days 2 through 6, and the proportion of patients hospitalized on day 29 was significantly lower with LY-CoV555 (1.6% vs. 6.3%). Of the potential effects on symptoms and hospitalizations, the authors write, “If these results are confirmed … LY-CoV555 could become a useful treatment for emergency use in patients with recently diagnosed COVID-19.”
Here is a link to the full article in case you want to read it. https://www.nejm.org/doi/full/10.1056/NEJMoa2029849?query=pfw&jwd=000100563204&jspc=IM